High-impact research with PILATUS and EIGER data

In 2016, EIGER and PILATUS contributed 163 structures to 74 Nature, Science and Cell publications.

In 2015, there were 73 papers in Nature, Science and Cell with 164 structures solved with PILATUS data.

74 High-resolution crystal structure of the human CB1 cannabinoid receptor.
Authors Shao Z, Yin J, Chapman K, Grzemska M, Clark L, Wang J, Rosenbaum DM.
Citation Nature. 2016 Dec 22;540(7634):602-6.
PDB codes 5U09
Equipment EIGER X 16M @ APS BL 23-ID-B
Summary Modulation of cannabinoid receptors has therapeutic potential to control pain, epilepsy, obesity and other disorders. The crystal structure of the human cannabinoid receptor CB1 bound to the inhibitor taranabant reveals an extracellular surface distinct from those of similar lipid-activated receptors and suggests ways to design and optimize therapeutic modulators of the endocannabinoid system.
73 Engineering extrinsic disorder to control protein activity in living cells.
Authors Dagliyan O, Tarnawski M, Chu PH, Shirvanyants D, Schlichting I, Dokholyan NV, Hahn KM.
Citation Science. 2016 Dec 16;354(6318):1441-4.
Equipment PILATUS 6M @ SLS BL X10SA
Summary Sensory domains inserted into nonconserved, surface-exposed loops that are allosterically coupled to active sites can switch proteins between active and inactive conformations to study their function. Four crystal structures show the broad applicability of this approach to the design of physiological protein switches.
72 Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists.
Authors Zheng Y, Qin L, Zacarías NV, de Vries H, Han GW, Gustavsson M, Dabros M, Zhao C, Cherney RJ, Carter P, Stamos D, Abagyan R, Cherezov V, Stevens RC, IJzerman AP, Heitman LH, Tebben A, Kufareva I, Handel TM.
Citation Nature. 2016 Dec 15;540(7633):458-61.
PDB codes 5T1A
Equipment PILATUS3 6M @ APS BL 23-ID-D
Summary CC chemokine receptor 2 (CCR2) is implicated in inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis and asthma, as well as cancer. The structure of CCR2 in complex with an orthosteric and an allosteric antagonist reveals a previously unseen binding mode and a novel binding pocket attractive for drug design.
71 Intracellular allosteric antagonism of the CCR9 receptor.
Authors Oswald C, Rappas M, Kean J, Doré AS, Errey JC, Bennett K, Deflorian F, Christopher JA, Jazayeri A, Mason JS, Congreve M, Cooke RM, Marshall FH.
Citation Nature. 2016 Dec 15;540(7633):462-5.
PDB codes 5LWE
Equipment PILATUS3 6M @ DLS BL I24
Summary Of over 50 chemokine antagonists that have entered clinical development as candidate drugs against G-protein-coupled receptors, only two have reached the market. The crystal structure of the CC chemokine receptor type 9 in complex with its antagonist vercirnon reveals the mechanism of action of chemokine antagonists and suggests ways to optimize compounds for improved drug design.
70 Electric-field-stimulated protein mechanics.
Authors Hekstra DR, White KI, Socolich MA, Henning RW, Šrajer V, Ranganathan R.
Citation Nature. 2016 Dec 15;540(7633):400-405.
PDB codes 5E1Y 5E21
Equipment PILATUS 6M @ SSRL BL 11-1
Summary Coordinated motions of atoms and the forces among them turn protein structure into function. The application of electric field pulses induces conformational changes in proteins that are here observed in spatial and temporal detail. The changes are consistent with what is induced by ligands, demonstrating a new way of studying the mechanical basis of protein function.
69 Crystal structures of a group II intron lariat primed for reverse splicing.
Authors Costa M, Walbott H, Monachello D, Westhof E, Michel F.
Citation Science. 2016 Dec 2;354(6316):aaf9258.
PDB codes 5J01 5J02
Summary Group II introns are genetically mobile ribozymes that can excise themselves from host RNA. Two crystal structures show the catalytic center of the ribozyme and the branched RNA conformation that is critical for splicing and rationalize the strong conservation of this architecture across evolution.
68 Phosphoribosylation of ubiquitin promotes serine ubiquitination and impairs conventional ubiquitination.
Authors Bhogaraju S, Kalayil S, Liu Y, Bonn F, Colby T, Matic I, Dikic I.
Citation Cell. 2016 Dec 1;167(6):1636-1649.e13.
PDB codes 5M93
Equipment PILATUS 2M @ SLS BL X06DA
Summary SdeA, an effector protein of pathogenic Legionella pneumophila, catalyzes arginine phosphoribosylation of ubiquitin, thus preventing activation of E1 and E2 enzymes of the conventional ubiquitination cascade. This might modulate ubiquitin functions in mammalian cells.
67 Structural mechanism for cargo recognition by the retromer complex.
Authors Lucas M, Gershlick DC, Vidaurrazaga A, Rojas AL, Bonifacino JS, Hierro A.
Citation Cell. 2016 Dec 1;167(6):1623-1635.e14.
PDB codes 5F0J 5F0K 5F0L 5F0M 5F0P
Summary Retromer recycles transmembrane cargo from endosomes. Defects in its function are implicated in Parkinson's and Alzheimer's diseases. Crystal structures of a complex of retromer subunits, a sorting protein and part of a recycled cargo protein identify a binding site for recycling signals and highlight cooperative interactions that couple signal recognition to membrane recruitment.
66 An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme.
Authors Ortmayer M, Lafite P, Menon BR, Tralau T, Fisher K, Denkhaus L, Scrutton NS, Rigby SE, Munro AW, Hay S, Leys D.
Citation Nature. 2016 Nov 24;539(7630):593-597.
PDB codes 5LTE 5LTH 5LTI
Equipment PILATUS 2M @ DLS BL I04-1
Summary The Per-ARNT-Sim (PAS) scaffold senses diverse stimuli like light and redox state and can bind a broad range of ligands, including haem, flavins and metal ions. Characterization of the first known enzyme based on the PAS domain shows an unusual amine oxidase and suggests that the PAS scaffold supports the development of artificial enzymes.
65 Structure of the MIS12 complex and molecular basis of its interaction with CENP-C at human kinetochores.
Authors Petrovic A, Keller J, Liu Y, Overlack K, John J, Dimitrova YN, Jenni S, van Gerwen S, Stege P, Wohlgemuth S, Rombaut P, Herzog F, Harrison SC, Vetter IR, Musacchio A.
Citation Cell. 2016 Nov 3;167(4):1028-40.
PDB codes 5LSI 5LSJ 5LSK
Summary Kinetochore complexes tether chromosomes to spindle microtubules to promote chromosome segregation during mitosis. The cocrystal structure of two kinetochore subcomplexes whose interaction is regulated by Aurora B-mediated phosphorylation illuminates the structural organization of the broadly conserved chromosome segregation machinery.
64 Structure of the MIND complex defines a regulatory focus for yeast kinetochore assembly.
Authors Dimitrova YN, Jenni S, Valverde R, Khin Y, Harrison SC.
Citation Cell. 2016 Nov 3;167(4):1014-27.
PDB codes 5T51 5T58 5T59 5T6J
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary The MIND complex, part of the kinetochore in budding yeast, mediates the connection between centromeric nucleosomes and the microtubules of the mitotic spindle. The crystal structure of the MIND complex and interaction studies reveal the elongated conformation of MIND and how phosphorylation regulates kinetochore assembly.
63 Arginine phosphorylation marks proteins for degradation by a Clp protease.
Authors Trentini DB, Suskiewicz MJ, Heuck A, Kurzbauer R, Deszcz L, Mechtler K, Clausen T.
Citation Nature. 2016 Nov 3;539(7627):48-53.
PDB codes 5HBN
Summary Arginine phosphorylation is shown as a mechanism by which proteins are targeted for degradation by the ClpC–ClpP complex in Gram-positive bacteria in a manner functionally analogous to the ubiquitin–proteasome system in eukaryotes. The regulator ClpC recognizes the phosphoarginine degradation tag by binding to its amino-terminal domain.
62 Pore architecture of TRIC channels and insights into their gating mechanism.
Authors Yang H, Hu M, Guo J, Ou X, Cai T, Liu Z.
Citation Nature. 2016 Oct 27;538(7626):537-41.
PDB codes 5EGI
Equipment PILATUS 2M @ Photon Factory BL 1A
Summary Trimeric intracellular cation (TRIC) channels are major players in Ca2+ signaling and homeostasis. Mutations are associated with hypertension and heart disease, among others. The crystal structures of two isoforms of TRIC complexed to lipid molecules suggest an ion permeation pathway and reveal a lipid-dependent gating mechanism.
61 The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models.
Authors Kotschy A, Szlavik Z, Murray J, Davidson J, Maragno AL, Le Toumelin-Braizat G, Chanrion M, Kelly GL, Gong JN, Moujalled DM, Bruno A, Csekei M, Paczal A, Szabo ZB, Sipos S, Radics G, Proszenyak A, Balint B, Ondi L, Blasko G, Robertson A, Surgenor A, Dokurno P, Chen I, Matassova N, Smith J, Pedder C, Graham C, Studeny A, Lysiak-Auvity G, Girard AM, Gravé F, Segal D, Riffkin CD, Pomilio G, Galbraith LC, Aubrey BJ, Brennan MS, Herold MJ, Chang C, Guasconi G, Cauquil N, Melchiore F, Guigal-Stephan N, Lockhart B, Colland F, Hickman JA, Roberts AW, Huang DC, Wei AH, Strasser A, Lessene G, Geneste O.
Citation Nature. 2016 Oct 27;538(7626):477-82.
PDB codes 5LOF
Summary S63845 is a small molecule that inhibits the pro-survival protein myeloid cell leukemia 1 (MCL1) which is critical for the avoidance of apoptosis and thus the sustained growth of tumors. S63845 binds with high specificity in the BH3-binding groove of MCL1 and potently kills a wide range of MCL1-dependent cancer cells.
60 Crystal structure of the human cannabinoid receptor CB1.
Authors Hua T, Vemuri K, Pu M, Qu L, Han GW, Wu Y, Zhao S, Shui W, Li S, Korde A, Laprairie RB, Stahl EL, Ho JH, Zvonok N, Zhou H, Kufareva I, Wu B, Zhao Q, Hanson MA, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ.
Citation Cell. 2016 Oct 20;167(3):750-762.
PDB codes 5TGZ
Equipment PILATUS3 6M @ SPring-8 BL 41XU
Summary Cannabinoid receptor 1 (CB1) interacts with the psychoactive chemical in Cannabis sativa and holds promise as a target for pain management and the therapy of inflammation and obesity. The crystal structure of CB1 in complex with an agonist provides insight into the binding mode of naturally ocurring ligands and provides leads for the design for novel CB1-targeting drugs.
59 X-ray structure of the human α4β2 nicotinic receptor.
Authors Morales-Perez CL, Noviello CM, Hibbs RE.
Citation Nature. 2016 Oct 20;538(7625);411-415.
PDB codes 5KXI
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary Nicotinic acetylcholine receptors mediate neutransmission in all vertebrates. High-resolution structural information has only been available on homopentameric channels. The crystal structure of the nicotinic acetylcholine receptor subtype from human brain, an α/β heteropentamer, provides insight into ligand recognition, assembly, ion permeation and desensitization.
58 Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne.
Authors Mevissen TE, Kulathu Y, Mulder MP, Geurink PP, Maslen SL, Gersch M, Elliott PR, Burke JE, van Tol BD, Akutsu M, El Oualid F, Kawasaki M, Freund SM, Ovaa H, Komander D.
Citation Nature. 2016 Oct 20;538(7625):402-5.
Equipment PILATUS 6M @ ESRF BLs ID23-1, ID29; PILATUS 6M @ DLS BL I02; PILATUS3 6M @ DLS BL I03
Summary The ovarian tumour family deubiquitinase Cezanne recognizes Lys11-linked polyubiquitin. Crystal structures of Cezanne alone and in complex with monoubiquitin and Lys11-linked polyubiquitin elucidate the enzymatic cycle, reveal conformational changes that activate the enzyme and highlight the plasticity of deubiquitinases.
57 The methanogenic CO2 reducing-and-fixing enzyme is bifunctional and contains 46 [4Fe-4S] clusters.
Authors Wagner T, Ermler U, Shima S.
Citation Science. 2016 Oct 7;354(6308):114-7.
PDB codes 5T5I 5T5M 5T61
Equipment PILATUS 6M @ SLS BL X10SA
Summary Archaea synthesize methane from CO2 and methanofuran (MFR) by way of a formyl-MRF intermediate. The tungsten-containing formyl-MFR dehydrogenase complex contains two active sites separated by long tunnel for the transfer of the formate. The 46 iron-sulfur clusters serve as an electron relay and may couple the four the tungsten redox centers.
56 Crystal structure of silkworm PIWI-clade Argonaute Siwi bound to piRNA.
Authors Matsumoto N, Nishimasu H, Sakakibara K, Nishida KM, Hirano T, Ishitani R, Siomi H, Siomi MC, Nureki O.
Citation Cell. 2016 Oct 6;167(2):484-97.
PDB codes 5GUH
Equipment PILATUS3 6M @ SPring-8 BL 41XU
Summary Argonaute proteins bind to RNA guides and silence transposable elements. The crystal structure of a PIWI-clade Argonaute protein bound to RNA shows clear differences to Ago-clade Argonaute proteins in nucleic acid binding but also surprising similarities with prokaryotic Ago-clade Argonaute proteins in terms of catalysis.
55 Structural insight into the role of the Ton complex in energy transduction.
Authors Celia H, Noinaj N, Zakharov SD, Bordignon E, Botos I, Santamaria M, Barnard TJ, Cramer WA, Lloubes R, Buchanan SK.
Citation Nature. 2016 Oct 6;538(7623):60-5.
PDB codes 5SV0
Equipment PILATUS3 6M @ APS BL 23-ID-D
Summary The multicomponent Ton complex, sitting in the inner membrane of Gram-negative bacteria, transduces energy for the import of nutrients by outer membrane transporters. Here, the stoichiometry of the complex is revealed and a mechanism of harnessing the protein motive force postulated.
54 X-ray structures define human P2X3 receptor gating cycle and antagonist action.
Authors Mansoor SE, Lü W, Oosterheert W, Shekhar M, Tajkhorshid E, Gouaux E.
Citation Nature. 2016 Oct 6;538(7623):66-71.
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary PX2 receptors, trimeric, nonselective cation channels activated by ATP, play central roles in human physiology and are potential drug targets. Here, four crystal structures of the PX23 receptor in the apo state, bound to an agonist in open- and close-pore conformations, and bound to an antagonist in a closed conformation illuminate receptor gating and provide a basis for drug development.
53 Directed evolution of artificial metalloenzymes for in vivo metathesis.
Authors Jeschek M, Reuter R, Heinisch T, Trindler C, Klehr J, Panke S, Ward TR.
Citation Nature. 2016 Sep 29;537(7622):661-5.
PDB codes 5IRA 5F2B
Equipment EIGER X 16M @ SLS BL X06SA
Summary Biocatalysis increasingly relies on directed evolution of desired enzymatic activities. Here, the evolution and assembly in vivo of a metalloenzyme for olefin metathesis, an archetypal organometallic reaction, is reported. The enzyme catalyses the abiotic reaction in vivo with increased throughput compared to conventional approaches.
52 HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis.
Authors Jacques DA, McEwan WA, Hilditch L, Price AJ, Towers GJ, James LC.
Citation Nature. 2016 Aug 18;536(7616):349-53.
PDB codes 5HGN 5JPA
Equipment PILATUS 6M @ DLS BL I02
Summary HIV capsid protects viral components as the virus matures but allows free access of nucleotides for RNA synthesis. This study shows that each capsid hexamer contains an arginine-lined pore that recruits nucleotides and can be obstructred by a channel blocker that inhibits reverse transcription in the capsid.
51 Mechanism of arginine sensing by CASTOR1 upstream of mTORC1.
Authors Saxton RA, Chantranupong L, Knockenhauer KE, Schwartz TU, Sabatini DM.
Citation Nature. 2016 Aug 11;536(7615):229-33.
PDB codes 5I2C
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary The amino acid arginine is an important input for mechanistic Target of Rapamycin Complex 1 (mTORC1), which controls anabolic and catabolic cellular processes in mammals. The structure of CASTOR1, a cellular arginine sensor for mTORC1, in complex with arginine establishes the structural basis for mammalian arginine sensing and provides insight into its evolution.
50 The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design.
Authors Schrader J, Henneberg F, Mata RA, Tittmann K, Schneider TR, Stark H, Bourenkov G, Chari A.
Citation Science. 2016 Aug 5;353(6299):594-8.
PDB codes 5LE5 5LEX 5LEY 5LEZ 5LF0 5LF1 5LF3 5LF4 5LF6 5LF7
Summary Proteasomes are complex regulated proteases and validated targets for anti-cancer therapy. Crystal structures of the human proteasome alone and in eight complexes with inhibitors provide insight into the mechanism of inhibition and a better description of the active sites. This will help with the design of novel cancer drugs targeting the proteasome.
49 Structural basis of potent Zika–dengue virus antibody cross-neutralization.
Authors Barba-Spaeth G, Dejnirattisai W, Rouvinski A, Vaney MC, Medits I, Sharma A, Simon-Lorière E, Sakuntabhai A, Cao-Lormeau VM, Haouz A, England P, Stiasny K, Mongkolsapaya J, Heinz FX, Screaton GR, Rey FA.
Citation Nature. 2016 Aug 4;536(7614):48-53.
PDB codes 5LBS 5LCV 5LBV
Summary Zika virus is a flavivirus associated with severe birth defects. Structures of the viral envelope protein with antibodies cross-reactive against Zika and Dengue provide a lead for epitope-focused design of a vaccine capable of protecting simultaneously against both Zika and dengue virus infections.
48 Structure of the adenosine A2A receptor bound to an engineered G protein.
Authors Carpenter B, Nehmé R, Warne T, Leslie AG, Tate CG.
Citation Nature. 2016 Aug 4;536(7614):104-7.
PDB codes 5G53
Equipment PILATUS 2M @ ESRF BL ID23-2
Summary A crystal structure of the adenosine A2A receptor bound to an engineered G protein shows that the transition between an agonist-bound active-intermediate state to an active G-protein-bound state is characterized by a 14 Å shift of a helix away from the receptor core and other minor changes.
47 Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor.
Authors Lei J, Hansen G, Nitsche C, Klein CD, Zhang L, Hilgenfeld R.
Citation Science. 2016 Jul 29;353(6298):503-5.
PDB codes 5LC0
Summary Cleavage of the viral polyprotein, an essential step during virus maturation, depends on Zika protease, which is thus an attractive target for future antiviral drugs. The crystal structure of Zika protease in complex with a peptido-mimetic inhibitor represents a promising starting point for drug design.
46 Structure and function analysis of an antibody recognizing all influenza A subtypes.
Authors Kallewaard NL, Corti D, Collins PJ, Neu U, McAuliffe JM, Benjamin E, Wachter-Rosati L, Palmer-Hill FJ, Yuan AQ, Walker PA, Vorlaender MK, Bianchi S, Guarino B, De Marco A, Vanzetta F, Agatic G, Foglierini M, Pinna D, Fernandez-Rodriguez B, Fruehwirth A, Silacci C, Ogrodowicz RW, Martin SR, Sallusto F, Suzich JA, Lanzavecchia A, Zhu Q, Gamblin SJ, Skehel JJ.
Citation Cell. 2016 Jul 28;166(3):596-608.
PDB codes 5JW3 5JW4 5JW5
Equipment PILATUS 6M @ DLS BL I02, I04
Summary Influenza A infections account for the majority of influenza hospitalizations and can cause pandemics. The development of a monoclonal antibody reactive against all influenza A hemagglutinin subtypes suggests great potential for immunotherapy of influenza virus-infected humans.
45 Structural basis of Smoothened regulation by its extracellular domains.
Authors Byrne EF, Sircar R, Miller PS, Hedger G, Luchetti G, Nachtergaele S, Tully MD, Mydock-McGrane L, Covey DF, Rambo RP, Sansom MS, Newstead S, Rohatgi R, Siebold C.
Citation Nature. 2016 Jul 28;535(7613):517-22.
PDB codes 5L7D 5L7I
Equipment PILATUS3 6M @ DLS BL I24
Summary Crystal structures of Smoothened, a G-protein coupled receptor important in transducing developmental signals, reveal two distinct ligand-binding sites in its transmembrane and extracellular cystein-rich domains. The structures clarify how ligand-regulated interactions between its two domains modulate the activity of Smoothened.
44 Accurate design of megadalton-scale two-component icosahedral protein complexes.
Authors Bale JB, Gonen S, Liu Y, Sheffler W, Ellis D, Thomas C, Cascio D, Yeates TO, Gonen T, King NP, Baker D.
Citation Science. 2016 Jul 22;353(6297):389-94.
PDB codes 4IM4 4IM5 4IM6
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary Using pairwise combinations of dimeric, trimeric, or pentameric building blocks, ten protein cages of three distinct icosahedral arrangements were computationally designed and experimentally characterized. These cages the size of small viruses hold promise for the controlled delivery of drugs and vaccines and for genetically programmable protein-based molecular machines.
43 The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA.
Authors Bird JG, Zhang Y, Tian Y, Panova N, Barvík I, Greene L, Liu M, Buckley B, Krásný L, Lee JK, Kaplan CD, Ebright RH, Nickels BE.
Citation Nature. 2016 Jul 21;535(7612):444-7.
PDB codes 5D4C
Equipment PILATUS 6M @ NSLS BL X29A
Summary In eukaryotes, RNA carries a 5′ 7-methylguanylate cap. Analogous caps composed of NAD+, NADH and 3′-desphospho-coenzyme A are incorporated into RNA during transcription initiation by prokaryotic and eukaryotic RNA polymerases. This study defines the mechanism and structural basis of capping with these non-canonical initiating nucleotides and suggests functional consequences.
42 Structural basis for integration of GluD receptors within synaptic organizer complexes.
Authors Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR.
Citation Science. 2016 Jul 15;353(6296):295-9.
PDB codes 5KC6 5KC7 5KC9 5KCA
Equipment PILATUS3 6M @ DLS BLs I03, I24; PILATUS 2M @ DLS BL I04-1
Summary By transmitting signals across the synapse, glutamate receptors are critical for the majority of cognitive functions. Crystal structures of complexes of presynaptic β-neurexin and postsynaptic glutamate receptor GluD2 show how this transsynaptic bridge is organized and how it promotes synaptogenesis and serine-dependent GluD2 signaling.
41 Pore-forming activity and structural autoinhibition of the gasdermin family.
Authors Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, Sun H, Wang DC, Shao F.
Citation Nature. 2016 Jul 07;535(7610):111-6.
PDB codes 5B5R
Equipment PILATUS3 6M @ SSRF BL 19U-1
Summary Gasidermin proteins bind lipids and can disrupt mammalian membranes to cause pyroptosis, a lytic form of cell death crucial for immune defences and diseases. The crystal structure of gasidermin A3 together with biochemical work reveals the mechanism behind pyroptosis and helps explain the protein's role in necrosis and immunity.
40 Toremifene interacts with and destabilizes the Ebola virus glycoprotein.
Authors Zhao Y, Ren J, Harlos K, Jones DM, Zeltina A, Bowden TA, Padilla-Parra S, Fry EE, Stuart DI.
Citation Nature. 2016 Jul 7;535(7610):169-72.
PDB codes 5JQ3 5JQ7 5JQB
Equipment PILATUS 6M @ DLS BL I02; PILATUS3 6M @ DLS BL I03
Summary Ebola virus glycoprotein (GP) is responsible for host cell attachment and is thus a prime target for drug development. Binding of the anticancer drug toremifene or the painkiller ibuprofen prevents membrane fusion between virus and host. Crystal structures of GP alone and in complex with either drug reveal the mechanism of inhibition and may guide the development of novel drugs against Ebola virus.
39 Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases.
Authors Chen YN, LaMarche MJ, Chan HM, Fekkes P, Garcia-Fortanet J, Acker MG, Antonakos B, Chen CH, Chen Z, Cooke VG, Dobson JR, Deng Z, Fei F, Firestone B, Fodor M, Fridrich C, Gao H, Grunenfelder D, Hao HX, Jacob J, Ho S, Hsiao K, Kang ZB, Karki R, Kato M, Larrow J, La Bonte LR, Lenoir F, Liu G, Liu S, Majumdar D, Meyer MJ, Palermo M, Perez L, Pu M, Price E, Quinn C, Shakya S, Shultz MD, Slisz J, Venkatesan K, Wang P, Warmuth M, Williams S, Yang G, Yuan J, Zhang JH, Zhu P, Ramsey T, Keen NJ, Sellers WR, Stams T, Fortin PD.
Citation Nature. 2016 Jul 7;535(7610):148-52.
PDB codes 5EHR
Equipment PILATUS 6M @ APS BL 17-ID
Summary Mutations in the ubiquitously expressed tyrosine phosphatase SHP2 are found in multiple cancer types. A highly potent, selective and orally bioavailable allosteric small-molecule inhibitor stabilizes SHP2 in an auto-inhibited conformation and inhibits the proliferation of cancer cells, demonstrating that reduction of SHP2 activity is a valid therapeutic approach for the treatment of cancers.
38 Crystal structure of the epithelial calcium channel TRPV6.
Authors Saotome K, Singh AK, Yelshanskaya MV, Sobolevsky AI.
Citation Nature. 2016 Jun 23;534(7608):506-11.
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary The crystal structure of a calcium-selective transient receptor potential channel – important for calcium homeostasis – helps explain calcium selectivity (determined by a filter of aspartate side chains) and suggests a calcium permeation mechanism.
37 Structure of IZUMO1–JUNO reveals sperm–oocyte recognition during mammalian fertilization.
Authors Ohto U, Ishida H, Krayukhina E, Uchiyama S, Inoue N, Shimizu T.
Citation Nature. 2016 Jun 23;534(7608):566-9.
Equipment PILATUS 2M @ Photon Factory BL AR-NE3A
Summary The sperm membrane protein IZUMO1 and its oocyte receptor JUNO are essential factors for sperm–oocyte interaction and fusion. Crystal structures of these two proteins and their complex establishes the structural basis of sperm–oocyte interaction and will contribute to the development of new therapeutic interventions for fertility.
36 Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex.
Authors Wang X, Feng J, Xue Y, Guan Z, Zhang D, Liu Z, Gong Z, Wang Q, Huang J, Tang C, Zou T, Yin P.
Citation Nature. 2016 Jun 23;534(7608):575-8.
PDB codes 5IL1 5IL2
Equipment PILATUS3 6M @ SSRF BL 19U-1
Summary Methylation of adenosine is an important regulatory modification of RNA. Crystal structures of a heterodimeric RNA methyltransferase in apo form and bound to ligand help assign catalytic function to one constituent of the dimer and target recognition to the other.
35 Structural basis of transcription activation.
Authors Feng Y, Zhang Y, Ebright RH.
Citation Science. 2016 Jun 10;352(6291):1330-3.
PDB codes 5I2D
Equipment PILATUS 6M @ NSLS BL X25
Summary The crystal structure of an intact bacterial class II transcription activation complex comprising RNA polymerase–σA, a transcription activator, promoter DNA and an RNA primer suggests that the activator stimulates the formation of an open transcriptionally active polymerase–promoter complex by stabilizing protein–protein interactions.
34 Activation of NMDA receptors and the mechanism of inhibition by ifenprodil.
Authors Tajima N, Karakas E, Grant T, Simorowski N, Diaz-Avalos R, Grigorieff N, Furukawa H.
Citation Nature. 2016 Jun 2;534(7605):63-8.
PDB codes 5B3J
Equipment PILATUS3 6M @ APS BL 23-ID-D
Summary N-methyl-D-aspartate receptors are essential for brain development and function. This study combined X-ray crystallography, single-particle electron cryomicroscopy and electrophysiology to show that, in the absence of the allosteric inhibitor ifenprodil, the receptor forms an active conformation that gates the ion channel.
33 Control of eukaryotic phosphate homeostasis by inositol polyphosphate sensor domains.
Authors Wild R, Gerasimaite R, Jung JY, Truffault V, Pavlovic I, Schmidt A, Saiardi A, Jessen HJ, Poirier Y, Hothorn M, Mayer A.
Citation Science. 2016 May 20;352(6288):986-90.
Summary SPX domains provide a basic binding surface for inositol polyphosphate signaling molecules whose concentration varies as a function of intracellular inorganic phosphate concentration, thus allowing cells to sense, respond to and regulate changing levels of this precursor to the essential macronutrient phosphorus.
32 Transcription initiation complex structures elucidate DNA opening.
Authors Plaschka C, Hantsche M, Dienemann C, Burzinski C, Plitzko J, Cramer P.
Citation Nature. 2016 May 19;533(7603):353-8.
PDB codes 5IP7 5IP9
Equipment PILATUS 6M @ SLS BL X06SA
Summary Transcription of eukaryotic genes starts with the assembly of an initiation complex of RNA polymerase (Pol) II and subsequent promoter DNA opening. Structures of initiation complexes with open and closed DNA suggest a unified model for transcription initiation with the trapping of open promoter DNA as key event.
31 Structure of the T4 baseplate and its function in triggering sheath contraction.
Authors Taylor NMI, Prokhorov NS, Guerrero-Ferreira RC, Shneider MM, Browning C, Goldie KN, Stahlberg H, Leiman PG.
Citation Nature. 2016 May 19;533(7603):346-52.
PDB codes 5IW9
Equipment PILATUS 6M @ SLS BL X06SA
Summary A combination of electron cryo-microscopy and X-ray crystallography reveals the structure of the baseplate, the complex at the heart of contractile tails that penetrate the host cell membrane during phage infection and bacterial toxin secretion.
30 Extra-helical binding site of a glucagon receptor antagonist.
Authors Jazayeri A, Doré AS, Lamb D, Krishnamurthy H, Southall SM, Baig AH, Bortolato A, Koglin M, Robertson NJ, Errey JC, Andrews SP, Teobald I, Brown AJ, Cooke RM, Weir M, Marshall FH.
Citation Nature. 2016 May 12;533(7602):274-7.
PDB codes 5EE7
Equipment PILATUS 6M @ DLS BL I04
Summary Glucagon, a peptide important for glucose homeostasis, is transduced by its receptor, a class B G-protein-coupled receptor and an important target for anti-diabetic drugs. The crystals structure of the receptor with an antagonist bound to a peripheral allosteric site provides opportunities for structure-based drug design.
29 Crystal structure of Cpf1 in complex with guide RNA and target DNA.
Authors Yamano T, Nishimasu H, Zetsche B, Hirano H, Slaymaker IM, Li Y, Fedorova I, Nakane T, Makarova KS, Koonin EV, Ishitani R, Zhang F, Nureki O.
Citation Cell. 2016 May 5;165(4):949-62.
PDB codes 5B43
Equipment EIGER X 16M @ SLS BL X06SA
Summary The crystal structure of the CRISPR-Cas endonuclease Cpf1 in complex with guide RNA and target DNA provides mechanistic insight into RNA-guided DNA cleavage by Cpf1 and establishes principles for rational engineering of the CRISPR-Cpf1 system for genome editing.
28 Structure of a bd oxidase indicates similar mechanisms for membrane-integrated oxygen reductases.
Authors Safarian S, Rajendran C, Müller H, Preu J, Langer JD, Ovchinnikov S, Hirose T, Kusumoto T, Sakamoto J, Michel H.
Citation Science. 2016 Apr 29;352(6285):583-6.
PDB codes 5DOQ 5IR6
Equipment PILATUS 6M @ SLS BL X10SA
Summary Cytochrome bd oxidases reduce oxygen and prevent oxidative stress in bacteria. The mechanism of dioxygen bond cleavage may be mechanistically similar to that of heme-copper-containing oxidases despite completely different structures.
27 Structure and organization of heteromeric AMPA-type glutamate receptors.
Authors Herguedas B, García-Nafría J, Cais O, Fernández-Leiro R, Krieger J, Ho H, Greger IH.
Citation Science. 2016 Apr 29;352(6285):aad3873.
PDB codes 5FWX 5FWY
Equipment PILATUS 2M @ DLS BL I04-1
Summary AMPA-type glutamate receptors are central mediators of rapid neurotransmission and synaptic plasticity. Structures of homodimers are known. The first structures of heterodimers reported here provide a framework for deciphering AMPA receptor architecture and signaling.
26 Crystal structure of the human σ1 receptor.
Authors Schmidt HR, Zheng S, Gurpinar E, Koehl A, Manglik A, Kruse AC.
Citation Nature. 2016 Apr 28;532(7600):527-30.
PDB codes 5HK1 5HK2
Equipment PILATUS3 6M @ APS BL 23-ID-D
Summary Human σ1 receptor is an evolutionarily isolated protein implicated in disorders like depression, drug addiction, and neuropathic pain. The crystal strucures reported here show a flat, hydrophobic surface likely to contact the membrane of the endoplasmic reticulum. The ligand-binding cavity is large and hydrophobic and shows remarkable plasticity in ligand recognition.
25 The crystal structure of Cpf1 in complex with CRISPR RNA.
Authors Dong, Ren K, Qiu X, Zheng J, Guo M, Guan X, Liu H, Li N, Zhang B, Yang D, Ma C, Wang S, Wu D, Ma Y, Fan S, Wang J, Gao N, Huang Z.
Citation Nature. 2016 Apr 28;532(7600):522-6.
PDB codes 5ID6
Equipment PILATUS3 6M @ SSRF BL 19U-1
Summary The CRISPR-Cpf1 system mediates DNA interference in human cells. It is similar to CRISPR-Cas9 RNA-guided adaptive immune systems in bacteria and archaea but differs in guide RNAs and substrate specificity. The crystal structure of Cpf1 bound to RNA reveals the RNA recognition mechanism and provides insight into RNA-guided substrate binding of Cpf1 – with implications for genome editing.
24 X-ray structures and mechanism of the human serotonin transporter.
Authors Coleman JA, Green EM, Gouaux E.
Citation Nature. 2016 Apr 21;532(7599):334-9.
PDB codes 5I74
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary Structures of serotonin transporter (SERT), a target for antidepressant and psychostimulant drugs like (S)-citalopram or paroxetine, show the transporter locked in an outward-open conformation. An additional allosteric site prevents ligand release from the central site. The structures define the mechanism of antidepressant action in SERT.
23 Architecture of the symmetric core of the nuclear pore.
Authors Lin DH, Stuwe T, Schilbach S, Rundlet EJ, Perriches T, Mobbs G, Fan Y, Thierbach K, Huber FM, Collins LN, Davenport AM, Jeon YE, Hoelz A.
Citation Science. 2016 Apr 15;352(6283):aaf1015.
PDB codes 5HAX 5HAY 5HAZ 5HB0 5HB1 5HB3 5HB4 5HB5 5HB7 5HB8
Equipment PILATUS3 6M @ APS BL 23-ID-D; PILATUS 6M @ SSRL BL 12-2
Summary Nuclear pores regulate transport between the nucleus and the cytoplasm. Into the known overall shape of a pore, individual components were reconstituted. Crystallization of overlapping fragments allowed the unambiguous assembly of a larger complex, which contains eight spokes spanning the nuclear envelope.
22 Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase.
Authors Petzold G, Fischer ES, Thomä NH.
Citation Nature. 2016 Apr 7;532(7597):127-30.
PDB codes 5FQD
Equipment PILATUS 6M @ SLS BL X10SA
Summary Immune modulatory drugs like thalidomiden and lenalidomide bind complex E3 ubiquitin ligases and inhibit ubiquitination of their substrates, but they also direct E3 ubiquitin ligases to other targets. This work shows how lenalidomide alters the specificity of the ligase and provides a mechanistic explanation for the selective efficacy of this drug in myelodysplastic syndrome.
21 HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.
Authors Jardine JG, Kulp DW, Havenar-Daughton C, Sarkar A, Briney B, Sok D, Sesterhenn F, Ereño-Orbea J, Kalyuzhniy O, Deresa I, Hu X, Spencer S, Jones M, Georgeson E, Adachi Y, Kubitz M, deCamp AC, Julien JP, Wilson IA, Burton DR, Crotty S, Schief WR.
Citation Science. 2016 Mar 25;351(6280):1458-63.
PDB codes 5IDL 5IES 5IF0 5IFA
Equipment PILATUS 6M @ SSRL BLs 11-1, 12-2
Summary Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs) against HIV. Here, a germline-targeting immunogen for bNAbs was developed that showed promise as a candidate human vaccine prime. Further shaping with subsequent immunogens may elicit bNAbs in people.
20 Mycocerosic acid synthase exemplifies the architecture of reducing polyketide synthases.
Authors Herbst DA, Jakob RP, Zähringer F, Maier T.
Citation Nature. 2016 Mar 23;531(7595):533-7.
PDB codes 5BP1 5BP2 5BP3 5BP4
Equipment PILATUS 6M @ SLS BL X06SA
Summary Polyketide synthetases are modular enzymes that produce natural products with important biological and pharmacological activities. The comprehensive architectural model derived from crystal structures of mycocerosic acid synthase enables functional dissection and re-engineering of polyketide synthetases.
19 Crystal structure of a substrate-engaged SecY protein-translocation channel.
Authors Li L, Park E, Ling J, Ingram J, Ploegh H, Rapoport TA.
Citation Nature. 2016 Mar 17;531(7594):395-9.
PDB codes 5EUL
Equipment PILATUS3 6M @ APS BL 23-ID-D
Summary Secretory signal sequences of diverse sequence and length are recognized by the SecY translocation channel. During translocation, the hydrophobic segments of signal sequences exit the lateral gate of the channel and dock at a specific site facing the lipid phase, thus mediating recognition.
18 Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5.
Authors Mavrakis KJ, McDonald ER 3rd, Schlabach MR, Billy E, Hoffman GR, deWeck A, Ruddy DA, Venkatesan K, Yu J, McAllister G, Stump M, deBeaumont R, Ho S, Yue Y, Liu Y, Yan-Neale Y, Yang G, Lin F, Yin H, Gao H, Kipp DR, Zhao S, McNamara JT, Sprague ER, Zheng B, Lin Y, Cho YS, Gu J, Crawford K, Ciccone D, Vitari AC, Lai A, Capka V, Hurov K, Porter JA, Tallarico J, Mickanin C, Lees E, Pagliarini R, Keen N, Schmelzle T, Hofmann F, Stegmeier F, Sellers WR.
Citation Science. 2016 Mar 11;351(6278):1208-13.
PDB codes 5FA5
Equipment PILATUS 6M @ APS BL 17-ID
Summary A number of human tumors exhibit changes in methionine metabolism caused by loss of the gene coding for 5-methylthioadenosine phosphorylase (MTAP). Loss of MTAP causes sensitivity of cancer cells to growth inhibition by suppressors of the arginine methyltransferase PRMT5. Inhibitors of RPMT5 might thus be developed into therapeutic agents for MTAP-deficient tumors.
17 Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana.
Authors Kintzer AF, Stroud RM.
Citation Nature. 2016 Mar 10;531(7593):258-64.
PDB codes 5DQQ
Equipment PILATUS 6M @ SSRL BL 12-2
Summary Eukaryotic voltage- and ligand-gated cation channels of the two-pore channel family contain two non-equivalent tandem pore-forming subunits that dimerize to form quasi-tetramers. The crystal structure of TPC1 explains voltage sensitivity and inhibition of the channel by luminal calcium.
16 Structural basis of outer membrane protein insertion by the BAM complex.
Authors Gu Y, Li H, Dong H, Zeng Y, Zhang Z, Paterson NG, Stansfeld PJ, Wang Z, Zhang Y, Wang W, Dong C.
Citation Nature. 2016 Mar 3;531(7592):64-9.
PDB codes 5D0O 5D0Q
Equipment PILATUS3 6M @ DLS BL I03
Summary Outer membrane proteins perform many fundamental biological processes in Gram-negative bacteria. They are inserted and folded into the outer membrane by the β-barrel assembly machinery whose structure is reported here in an inward-open state and a lateral-open state.
15 Priming and polymerization of a bacterial contractile tail structure.
Authors Zoued A, Durand E, Brunet YR, Spinelli S, Douzi B, Guzzo M, Flaugnatti N, Legrand P, Journet L, Fronzes R, Mignot T, Cambillau C, Cascales E.
Citation Nature. 2016 Mar 3;531(7592):59-63.
PDB codes 4YO3 4YO5
Summary The bacterial type VI secretion system relies on a contractile sheath around a rigid inner tube to inject toxins into target cells. A dodecameric complex of TssA protein initiates tail polymerization, remains at the tip of the growing structure and incorporates new tube and sheath blocks.
14 Structure and engineering of Francisella novicida Cas9.
Authors Hirano H, Gootenberg JS, Horii T, Abudayyeh OO, Kimura M, Hsu PD, Nakane T, Ishitani R, Hatada I, Zhang F, Nishimasu H, Nureki O.
Citation Cell. 2016 Feb 25;164(5):950-61.
PDB codes 5B2O 5B2P 5B2Q
Equipment PILATUS3 6M @ SPring-8 BL 41XU
Summary Comparison of the structure of Francisella novicida Cas9 in complex with guide RNA and target DNA with flanking protospacers adjacent motifs (PAMs) with various orthologs reveals features important for PAM recognition.
13 Structural basis for promiscuous PAM recognition in type I-E Cascade from E. coli.
Authors Hayes RP, Xiao Y, Ding F, van Erp PB, Rajashankar K, Bailey S, Wiedenheft B, Ke A.
Citation Nature. 2016 Feb 25;530(7591):499-503.
PDB codes 5H9E 5H9F
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary During RNA-based adaptive immune response against foreign genetic elements in prokaryotes, CRISPR-associated complex for antiviral defence binds to foreign double-stranded DNA. A motif of flanking DNA is crucial for discrimination of self versus foreign. The structures in this paper rationalize the promiscuity and specificity of this process.
12 Structural basis for activity regulation of MLL family methyltransferases.
Authors Li Y, Han J, Zhang Y, Cao F, Liu Z, Li S, Wu J, Hu C, Wang Y, Shuai J, Chen J, Cao L, Li D, Shi P, Tian C, Zhang J, Dou Y, Li G, Chen Y, Lei M.
Citation Nature. 2016 Feb 25;530(7591):447-52.
PDB codes 5F5E
Equipment PILATUS3 6M @ SSRF BL 19U-1
Summary Mixed lineage leukaemia (MLL) proteins methylate histone lysines to regulate haematopoiesis and development. This works demonstrates a two-step activation mechanism of MLL proteins and suggests a universal mechanism of regulation of histone methyltransferases.
11 Structural basis of lipoprotein signal peptidase II action and inhibition by the antibiotic globomycin.
Authors Vogeley L, El Arnaout T, Bailey J, Stansfeld PJ, Boland C, Caffrey M.
Citation Science. 2016 Feb 19;351(6275):876-80.
PDB codes 5DIR
Equipment PILATUS 6M @ SLS BL X10SA
Summary The crystal structure of LspA, an aspartyl signal peptidase involved in the processing of bacterial lipoproteins, bound to the antibiotic globomycin gives clues as to the rational design of new antibiotics.
10 Crystal structure of the Rous sarcoma virus intasome.
Authors Yin Z, Shi K, Banerjee S, Pandey KK, Bera S, Grandgenett DP, Aihara H.
Citation Nature. 2016 Feb 18;530(7590):362-6.
PDB codes 5EJK
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary Integrase mediates the integration of reverse-transcribed retroviral DNA into the host genome. The crystal structure of the three-domain integrase from Rous sarcoma virus shows an octameric assembly with a pair of integrase dimers engaging viral DNA ends for catalysis and another pair helping to capture target DNA.
9 Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function.
Authors Ballandras-Colas A, Brown M, Cook NJ, Dewdney TG, Demeler B, Cherepanov P, Lyumkis D, Engelman AN.
Citation Nature. 2016 Feb 18;530(7590):358-61.
PDB codes 5CZ2 5D7U
Equipment PILATUS3 6M @ DLS BL I03
Summary A combination of cryo-EM and crystallographic work shows integrase, the enzyme that mediates integration into the host genome of reverse-transcribed retroviral DNA, with an unexpected octameric architecture. The peripheral two integrase dimers, though not conserved in retroviruses in general, are important for enzymatic activity in orthoretroviruses, the genus that includes all known pathogenic retroviruses.
8 Structural basis for histone H2B deubiquitination by the SAGA DUB module.
Authors Morgan MT, Haj-Yahya M, Ringel AE, Bandi P, Brik A, Wolberger C.
Citation Science. 2016 Feb 12;351(6274):725-8.
PDB codes 4ZUX
Equipment PILATUS3 6M @ APS BL 23-ID-D
Summary The covalent addition of ubiquitin to the nucleosome component H2B activates transcription. In contrast, removal of ubiquitin, for example by the SAGA complex, is associated with transcriptional inhibition. The structure suggests that ubiquitin can be removed at multiple stages of nucleosome disassembly and reassembly during transcription.
7 Structures of aminoarabinose transferase ArnT suggest a molecular basis for lipid A glycosylation.
Authors Petrou VI, Herrera CM, Schultz KM, Clarke OB, Vendome J, Tomasek D, Banerjee S, Rajashankar KR, Belcher Dufrisne M, Kloss B, Kloppmann E, Rost B, Klug CS, Trent MS, Shapiro L, Mancia F.
Citation Science. 2016 Feb 5;351(6273):608-12.
PDB codes 5F15 5EZM
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary Crystal structures of ArnT, a bacterial enzyme that mediates resistance to polymoxin antibiotics, one of the last lines of defense against combat multidrug-resistant infections, suggest a mechanism of action that might guide the design of better antibiotics.
6 Structure of a HOIP/E2–ubiquitin complex reveals RBR E3 ligase mechanism and regulation.
Authors Lechtenberg BC, Rajput A, Sanishvili R, Dobaczewska MK, Ware CF, Mace PD, Riedl SJ.
Citation Nature. 2016 Jan 28;529(7587):546-50.
PDB codes 5EDV
Equipment PILATUS3 6M @ APS BL 23-ID-D
Summary Members of the RING-between-RING (RBR) family of RING-type E3 ligases form covalent bonds with ubiquitin. The structure of an RBR in complex with an E2–ubiquitin conjugate reveal critical states of the E3 ligase cycle and suggests a general mechanism for RBR E3 ligases.
5 Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53.
Authors Martinez-Zapien D, Ruiz FX, Poirson J, Mitschler A, Ramirez J, Forster A, Cousido-Siah A, Masson M, Vande Pol S, Podjarny A, Travé G, Zanier K.
Citation Nature. 2016 Jan 28;529(7587):541-5.
PDB codes 4XR8
Equipment PILATUS 2M @ SLS BL X06DA
Summary The complex between the viral oncoprotein E6 from human papilloma virus (HPV) type 16, the LxxLL motif of the cellular ubiquitin ligase E6AP and the core domain of the human tumor suppressor protein p53 represents a prototype of viral hijacking of cellular pathways and provides a framework for the design of inhibitors against oncogenesis mediated by HPV.
4 Ebola viral glycoprotein bound to its endosomal receptor Niemann-Pick C1.
Authors Wang H, Shi Y, Song J, Qi J, Lu G, Yan J, Gao GF.
Citation Cell. 2016 Jan 14;164(1-2):258-68.
PDB codes 5F1B
Equipment PILATUS3 6M @ SSRF BL 19U-1
Summary The endosomal protein Niemann-Pick C1 (NPC1) is a necessary entry receptor for Ebola virus. The crystal structure of the primed glycoprotein (GPcl) of Ebola virus bound to domain C of NPC1 provides structural insights into filovirus entry in the late endosome and the molecular basis for design of therapeutic inhibitors of viral entry.
3 Crystal structure of a DNA catalyst.
Authors Ponce-Salvatierra A, Wawrzyniak-Turek K, Steuerwald U, Höbartner C, Pena V.
Citation Nature. 2016 Jan 14;529(7585):231-4.
PDB codes 5CKI 5CKK
Equipment PILATUS 6M @ SLS BL X10SA
Summary The first structure of a synthetic RNA-ligating DNA catalyst captures the ligation reaction in the post-catalytic state and reveals an unanticipated organization of the catalytic center. The structure highlights how the specific properties of deoxyribose are reflected in the backbone conformation of the DNA catalyst.
2 Architecture of human mTOR complex 1.
Authors Aylett CH, Sauer E, Imseng S, Boehringer D, Hall MN, Ban N, Maier T.
Citation Science. 2016 Jan 1;351(6268):48-52.
PDB codes 5EF5
Equipment PILATUS 6M @ SLS BL X06SA
Summary Dysregulation of the conserved protein kinase TOR is implicated in diabetes, cancer, and neurodegeneration. The structure of mammalian TOR in complex with subunits Raptor and mLST8 bound to FK506 binding protein (FKBP)–rapamycin, solved by combining cryo EM and X-ray crystallography, explains how architectural elements limit access to the recessed active site.
1 Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway.
Authors Saxton RA, Knockenhauer KE, Wolfson RL, Chantranupong L, Pacold ME, Wang T, Schwartz TU, Sabatini DM.
Citation Science. 2016 Jan 1;351(6268):53-8.
PDB codes 5DJ4
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary mTOR complex 1 regulates cellular growth based on nutrient availability. The crystal structure of the associated leucine sensor Sestrin2 shows how both the charged functional groups and the hydrophobic side chain of the amino acid are recognized specifically. Mutations in Sestrin2 lead to a increase in the leucine concentration required for mTORC1 activation in cells.