High-impact research with PILATUS and EIGER data

So far in 2017, EIGER and PILATUS contributed 74 structures to 30 Nature, Science and Cell publications.

30 Assembly principles and structure of a 6.5-MDa bacterial microcompartment shell.
Authors Sutter M, Greber B, Aussignargues C, Kerfeld CA.
Citation Science. 2017 Jun 23;356(6344):1293-7.
PDB codes 5V74
Equipment PILATUS 6M @ SSRL BL 12-2
Summary Many bacteria contain primitive proteinaceous organelles whose shells sequester enzymatic reactions from the cytosol. The crystal structure of an intact shell from Haliangium ochraceum reveals the basic principles of bacterial microcompartment shell construction, which might be used, eventually, in the design of artificial subcellular nanoreactors.
29 Structure of the Cpf1 endonuclease R-loop complex after target DNA cleavage.
Authors Stella S, Alcón P, Montoya G.
Citation Nature. 2017 Jun 22;546(7659):559-63.
PDB codes 5MGA
Equipment EIGER X 16M @ SLS BL X06SA
Summary The CRISPR nuclease Cpf1 holds high hopes as a genome-editing tool. Analysis of the structure of Cpf1 with the triple-stranded R-loop generated after DNA cleavage reveals the machinery involved in DNA unwinding, proposes a singular working model of RNA-guided DNA cleavage and suggests avenues for the redesign of Cpf1.
28 Structural basis of egg coat-sperm recognition at fertilization.
Authors Raj I, Al Hosseini HS, Dioguardi E, Nishimura K, Han L, Villa A, de Sanctis D, Jovine L.
Citation Cell. 2017 Jun 17;169(7):1315-26.e17.
PDB codes 5II4 5II5 5II6 5II7 5II8 5II9 5IIA 5IIB 5IIC 5MR2 5MR3
Equipment PILATUS 6M @ ESRF BLs ID23-1, ID29; PILATUS3 2M @ ESRF BL ID23-2; PILATUS 200K @ Rigaku Compact HomeLab
Summary Recognition between proteins in sperm and on the egg surface marks the beginning sexual reproduction. Structures of the invertebrate egg coat protein VERL and its complex with the sperm protein lysin illuminate gamete recognition and the molecular basis of gamete complementarity and sperm penetration during fertilization.
27 Structural basis of CRISPR–SpyCas9 inhibition by an anti-CRISPR protein.
Authors Dong D, Guo M, Wang S, Zhu Y, Wang S, Xiong Z, Yang J, Xu Z, Huang Z.
Citation Nature. 2017 Jun 15;546(7658):436-439.
PDB codes 5XBL
Equipment PILATUS3 6M @ SSRF BL 19U1
Summary CRISPR–Cas9 systems are bacterial adaptive immune systems that work by the targeted degradation of DNA. The structure of a Cas9 nuclease bound to guide RNA and the anti-CRISPR proteins AcrIIA2 shows that the inhibitor blocks DNA recognition and the endonuclease activity of Cas9.
26 Structure of the full-length glucagon class B G-protein-coupled receptor.
Authors Zhang H, Qiao A, Yang D, Yang L, Dai A, de Graaf C, Reedtz-Runge S, Dharmarajan V, Zhang H, Han GW, Grant TD, Sierra RG, Weierstall U, Nelson G, Liu W, Wu Y, Ma L, Cai X, Lin G, Wu X, Geng Z, Dong Y, Song G, Griffin PR, Lau J, Cherezov V, Yang H, Hanson MA, Stevens RC, Zhao Q, Jiang H, Wang MW, Wu B.
Citation Nature. 2017 Jun 8;546(7657):259-64.
PDB codes 5XF1
Equipment PILATUS3 6M @ SPring-8 BL 41XU
Summary The crystal structure of full-length human glucagon receptor, a G protein-coupled receptor important in glucose homeostasis and the pathophysiology of type 2 diabetes, illuminates the signaling mechanisms of G protein-coupled receptors.
25 Crystal structure of the GLP-1 receptor bound to a peptide agonist.
Authors Jazayeri A, Rappas M, Brown AJH, Kean J, Errey JC, Robertson NJ, Fiez-Vandal C, Andrews SP, Congreve M, Bortolato A, Mason JS, Baig AH, Teobald I, Doré AS, Weir M, Cooke RM, Marshall FH.
Citation Nature. 2017 Jun 8;546(7657):254-8.
PDB codes 5NX2
Equipment PILATUS3 6M @ DLS BL I24
Summary Agonists of glucagon-like peptide 1 (GLP-1), which regulates glucose homeostasis through the control of insulin release from the pancreas, are efficacious drugs for the treatment of diabetes. The crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist aided the design of peptide agonists with potent in vivo activity in a mouse model of diabetes.
24 Structural basis for antibody-mediated neutralization of Lassa virus.
Authors Hastie KM, Zandonatti MA, Kleinfelter LM, Heinrich ML, Rowland MM, Chandran K, Branco LM, Robinson JE, Garry RF, Saphire EO.
Citation Science. 2017 Jun 2;356(6341):923-8.
PDB codes 5VK2
Equipment PILATUS 6M @ SSRL BL 12-2
Summary Lassa virus causes severe, sometimes fatal, hemorrhagic fever. The viral surface glycoprotein GPC is the only antigen. The crystal structure of the GPC ectodomain bound to a neutralizing antibody from a human Lassa survivor provides a template for vaccine design.
23 Core Mediator structure at 3.4 Å extends model of transcription initiation complex.
Authors Nozawa K, Schneider TR, Cramer P.
Citation Nature. 2017 May 11;545(7653):248-51.
PDB codes 5N9J
Summary The crystal structure of mediator, a co-activator that binds the transcription pre-initiation complex and regulates RNA polymerase, provides a framework for understanding its function, including its role in stimulating phosphorylation of RNA polymerase by transcription initiation factor IIH.
22 Impact of cytosine methylation on DNA binding specificities of human transcription factors.
Authors Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, Das PK, Kivioja T, Dave K, Zhong F, Nitta KR, Taipale M, Popov A, Ginno PA, Domcke S, Yan J, Schübeler D, Vinson C, Taipale J.
Citation Science. 2017 May 5;356(6337):eaaj2239
PDB codes 5LUX 5EF6 5HOD
Equipment PILATUS 6M @ ESRF BLs ID23-1, ID29
Summary Methylation of the cytosine in pairs of cytosine and guanine (GpC) in DNA alters DNA structure and can inhibit transcription factor (TF) binding. Crystal structures of three TFs whose binding is stimulated by GpC methylation reveal the molecular determinants of this unexpected interaction.
21 Recurrent potent human neutralizing antibodies to Zika virus in Brazil and Mexico.
Authors Robbiani DF, Bozzacco L, Keeffe JR, Khouri R, Olsen PC, Gazumyan A, Schaefer-Babajew D, Avila-Rios S, Nogueira L, Patel R, Azzopardi SA, Uhl LFK, Saeed M, Sevilla-Reyes EE, Agudelo M, Yao KH, Golijanin J, Gristick HB, Lee YE, Hurley A, Caskey M, Pai J, Oliveira T, Wunder EA Jr, Sacramento G, Nery N Jr, Orge C, Costa F, Reis MG, Thomas NM, Eisenreich T, Weinberger DM, de Almeida ARP, West AP Jr, Rice CM, Bjorkman PJ, Reyes-Teran G, Ko AI, MacDonald MR, Nussenzweig MC.
Citation Cell. 2017 May 4;169(4):597-609.e11.
PDB codes 5VIC 5VIG
Equipment PILATUS 6M @ SSRL BL 12-2
Summary Zika virus causes severe birth defects. Individuals exposed to Dengue virus before they encounter Zika virus produce high levels of cross-neutralizing antibodies. Crystal structures reveal the mechanism of binding of these antibodies to Zika virus envelope domain III.
20 Structural insight into allosteric modulation of protease-activated receptor 2.
Authors Cheng RKY, Fiez-Vandal C, Schlenker O, Edman K, Aggeler B, Brown DG, Brown GA, Cooke RM, Dumelin CE, Doré AS, Geschwindner S, Grebner C, Hermansson NO, Jazayeri A, Johansson P, Leong L, Prihandoko R, Rappas M, Soutter H, Snijder A, Sundström L, Tehan B, Thornton P, Troast D, Wiggin G, Zhukov A, Marshall FH, Dekker N.
Citation Nature. 2017 May 4;545(7652):112-5.
PDB codes 5NDD 5NDZ 5NJ6
Equipment PILATUS3 6M at DLS BL I24; PILATUS 6M at ESRF BL ID29
Summary Protease-activated receptors (PARs) are implicated in cancer and inflammation and attractive targets for pharmaceutical research. The crystal structures of PAR2 in complex with two distinct antagonists and a blocking antibody show how receptor activation relies on structural rearrangements and access. The structures provide a basis for the development of selective PAR2 antagonists.
19 Structure and allosteric inhibition of excitatory amino acid transporter 1.
Authors Canul-Tec JC, Assal R, Cirri E, Legrand P, Brier S, Chamot-Rooke J, Reyes N.
Citation Nature. 2017 Apr 27;544(7651):446-51.
PDB codes 5MJU 5LLM 5LLU
Summary Dysregulation of transporters of excitatory neurotransmitters is associated with neurodegenerative disorders and cancer. Crystal structures of one such transporter, excitatory amino acid transporter 1, in its free form and bound to allosteric and competitive inhibitors, elucidate molecular details of its function and pharmacology.
18 A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis.
Authors Bridwell-Rabb J, Zhong A, Sun HG, Drennan CL, Liu HW.
Citation Nature. 2017 Apr 20;544(7650):322-6.
PDB codes 5UL2 5UL3 5UL4
Equipment PILATUS 6M @ APS BL 24-ID-C
Summary The potent antitumour, antiviral and antibacterial compound oxetanocin A is derived from a 2′-deoxyadenosine phosphate in a reaction catalyzed by a phosphohydrolase and an S-adenosylmethionine radical enzyme. Crystal structures of one of the enzymes bound to its cofactors illuminate the reaction mechanism and provide a framework for understanding the interplay of the cofactors.
17 Structural basis for selectivity and functional diversity in angiotensin II receptors.
Authors Zhang H, Han GW, Batyuk A, Ishchenko A, White KL, Patel N, Sadybekov A, Zamlynny B, Rudd MT, Hollenstein K, Tolstikova A, White TA, Hunter MS, Weierstall U, Liu W, Babaoglu K, Moore EL, Katz RD, Shipman JM, Garcia-Calvo M, Sharma S, Sheth P, Soisson SM, Stevens RC, Katritch V, Cherezov V.
Citation Nature. 2017 Apr 20;544(7650):327-32.
PDB codes 5UNH
Equipment PILATUS3 6M @ APS BL 23-ID-D
Summary The precise function of the angiotensin II receptor AT1R in the renin-angiotensin-aldosterone system is not clear. Two crystal structures of AT1R in complex with a specific and a broad ligand capture the receptor in an active-like conformation and show interactions crucial for ligand binding and selectivity. The results may guide the design of new selective ligands.
16 Crystal structure of the overlapping dinucleosome composed of hexasome and octasome.
Authors Kato D, Osakabe A, Arimura Y, Mizukami Y, Horikoshi N, Saikusa K, Akashi S, Nishimura Y, Park SY, Nogami J, Maehara K, Ohkawa Y, Matsumoto A, Kono H, Inoue R, Sugiyama M, Kurumizaka H.
Citation Science. 2017 Apr 14;356(6334):205-8.
PDB codes 5GSE
Equipment PILATUS3 6M @ SPring-8 BL 41XU
Summary Nucleosomes help package DNA in the tight space of the nucleus. Nucleosome repositioning is required for replication and transcription. This sometimes causes collisions. The crystal structure of a dinucleosome may represent an intermediate during these dynamic processes.
15 Structural insights into adiponectin receptors suggest ceramidase activity.
Authors Vasiliauskaité-Brooks I, Sounier R, Rochaix P, Bellot G, Fortier M, Hoh F, De Colibus L, Bechara C, Saied EM, Arenz C, Leyrat C, Granier S.
Citation Nature. 2017 Apr 6;544(7648):120-3.
PDB codes 5LX9 5LXA
Equipment PILATUS3 6M @ ESRF BL ID30B
Summary Adiponectin receptors (ADIPOR) control glucose and lipid metabolism by mediating a cellular ceramidase activity whose precise nature is not known. Crystal structures and functional studies show that both ADIPOR1 and ADIPOR2 possess basal ceramide activity. The two distinct structures may represent key steps in the enzymatic activity of ADIPORs.
14 Complex pectin metabolism by gut bacteria reveals novel catalytic functions.
Authors Ndeh D, Rogowski A, Cartmell A, Luis AS, Baslé A, Gray J, Venditto I, Briggs J, Zhang X, Labourel A, Terrapon N, Buffetto F, Nepogodiev S, Xiao Y, Field RA, Zhu Y, O'Neill MA, Urbanowicz BR, York WS, Davies GJ, Abbott DW, Ralet MC, Martens EC, Henrissat B, Gilbert HJ.
Citation Nature. 2017 Apr 6;544(7648):65-70.
Equipment PILATUS 6M @ DLS BLs I02, I04; PILATUS3 6M @ DLS BL I03; PILATUS 2M @ DLS BL I04-1
Summary Microbes in the human gut feed on complex dietary carbohydrates. Using previously undiscovered enzyme families and catalytic activities, Bacteroides thetaiotaomicron degrades the plant polysaccharide rhamnogalacturonan-II. The system of trimming side chains and backbone is described structurally and functionally.
13 Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites.
Authors Dawidowski M, Emmanouilidis L, Kalel VC, Tripsianes K, Schorpp K, Hadian K, Kaiser M, Mäser P, Kolonko M, Tanghe S, Rodriguez A, Schliebs W, Erdmann R, Sattler M, Popowicz GM.
Citation Science. 2017 Mar 31;355(6332):1416-20.
PDB codes 5L87 5L8A 5N8V
Summary Trypanosoma parasites cause sleeping sickness, Chagas disease, and leishmaniases. Crystal structures and nuclear magnetic resonance data enabled the design of small molecules that block glycosomal/peroxisomal import by disrupting a critical protein–protein interaction and selectively kill Trypanosoma, promising new, effective therapies.
12 The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1.
Authors Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, Marzinzik AL, Pelle X, Donovan J, Zhu W, Buonamici S, Hassan AQ, Lombardo F, Iyer V, Palmer M, Berellini G, Dodd S, Thohan S, Bitter H, Branford S, Ross DM, Hughes TP, Petruzzelli L, Vanasse KG, Warmuth M, Hofmann F, Keen NJ, Sellers WR.
Citation Nature. 2017 Mar 30;543(7647):733-7.
PDB codes 5MO4
Equipment PILATUS 6M @ SLS BL X10SA
Summary Chronic myeloid leukaemia (CML) is driven by the activity of the BCR–ABL1 fusion oncoprotein. A crystal structure of asciminib, a potent and selective allosteric ABL1 inhibitor currently undergoing clinical testing, shows that it binds to a secondary site, opening the possibility of combination therapy to avoid resistance mutations.
11 Structural basis of RNA polymerase I transcription initiation.
Authors Engel C, Gubbey T, Neyer S, Sainsbury S, Oberthuer C, Baejen C, Bernecky C, Cramer P.
Citation Cell. 2017 Mar 23;169(1):120-31.e22.
PDB codes 5N5X
Equipment EIGER 16M @ SLS BL X06SA
Summary A combined study of electron cryo-microscopy and X-ray crystallography reveals how RNA polymerase I and the initiation factors Rrn3 and core factor come together at the ribosomal RNA promoter during transcription initiation. Promoter specificity relies on contacts between initiation factors, DNA and polymerase enabled by pliability and dynamic melting of the promoter sequence.
10 Reversion of antibiotic resistance in Mycobacterium tuberculosis by spiroisoxazoline SMARt-420.
Authors Blondiaux N, Moune M, Desroses M, Frita R, Flipo M, Mathys V, Soetaert K, Kiass M, Delorme V, Djaout K, Trebosc V, Kemmer C, Wintjens R, Wohlkönig A, Antoine R, Huot L, Hot D, Coscolla M, Feldmann J, Gagneux S, Locht C, Brodin P, Gitzinger M, Déprez B, Willand N, Baulard AR.
Citation Science. 2017 Mar 17;355(6330):1206-11.
PDB codes 5ICJ 5N1I
Summary Some key antituberculosis antibiotics are delivered as inactive precursors. Resitance mutations often disable the biochemical pathways that produce the active antibiotic. Here, a secondary pathway for the activation of the antibiotic ethionamide is characterized. A small molecule targeting this pathway clears ethionamide-resistant infection in mice.
9 5' end nicotinamide adenine dinucleotide cap in human cells promotes RNA decay through DXO-mediated deNADding.
Authors Jiao X, Doamekpor SK, Bird JG, Nickels BE, Tong L, Hart RP, Kiledjian M.
Citation Cell. 2017 Mar 9;168(6):1015-27.e10.
PDB codes 5ULI
Equipment PILATUS3 6M @ APS BL 24-ID-C
Summary Mammalian mRNA may carry a 5' end nicotinamide adenine dinucleotide (NAD+) cap that promotes mRNA decay. A cocrystal structure of the enzyme that removes this cap with 3'-NADP+ illuminates the molecular mechanism of the reaction.
8 The cytotoxic Staphylococcus aureus PSMα3 reveals a cross-α amyloid-like fibril.
Authors Tayeb-Fligelman E, Tabachnikov O, Moshe A, Goldshmidt-Tran O, Sawaya MR, Coquelle N, Colletier JP, Landau M.
Citation Science. 2017 Feb 24;355(6327):831-3.
PDB codes 5I55
Equipment PILATUS3 6M @ APS BL 24-ID-C
Summary The 22-residue phenol-soluble modulin α3 (PSMα3) is secreted by Staphylococcus aureus as a highly toxic functional peptide. Its distinctive cross-α architecture, reminiscent of amyloid, facilitates toxicity and is likely to underly function in S. aureus.
7 Molecular mechanism for the regulation of yeast separase by securin.
Authors Luo S, Tong L.
Citation Nature. 2017 Feb 9;542(7640):255-9.
PDB codes 5U1T
Equipment PILATUS3 6M @ APS BL 24-ID-C
Summary The serine protease separase is important for sister chromatid segregation during mitosis. Its activity is suppressed by the regulator securin. The first crystal structure of a separase–securin complex defines interactions critical for inhibition and the stability of the complex.
6 DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair.
Authors Sibanda BL, Chirgadze DY, Ascher DB, Blundell TL.
Citation Science. 2017 Feb 3;355(6324):520-4.
PDB codes 5LUQ
Equipment PILATUS 6M @ ESRF BLs ID23-1, ID29
Summary Repair of DNA double-strand breaks is important to avoid cell death or cancer. The structure of the DNA-dependent kinase catalytic subunit bound to a C-terminal peptide of Ku80, a recruitment factor, suggests an allosteric mechanism of kinase activation. Competition between Ku80 and the tumor suppressor BRCA1 selects different pathways of DNA repair.
5 Structural basis for nutrient acquisition by dominant members of the human gut microbiota.
Authors Glenwright AJ, Pothula KR, Bhamidimarri SP, Chorev DS, Baslé A, Firbank SJ, Zheng H, Robinson CV, Winterhalter M, Kleinekathöfer U, Bolam DN, van den Berg B.
Citation Nature. 2017 Jan 19;541(7637):407-11.
PDB codes 5FQ3 5FQ4 5FQ6 5FQ7 5FQ8 5T4Y 5T3R
Equipment PILATUS3 6M @ DLS BLs I03, I24; PILATUS 6M @ DLS BL I04
Summary Microorganisms in the human gut play important roles in health and nutrition. They feed on dietary glycans that humans cannot metabolize. Here, the crystal structures of two bacterial glycan transporters give insight into how nutrients are imported across the outer membrane of human gut microbes.
4 Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms.
Authors Costa KC, Glasser NR, Conway SJ, Newman DK.
Citation Science. 2017 Jan 13;355(6321):170-3.
PDB codes 5K21
Equipment PILATUS 6M @ SSRL BL 12-2
Summary Pyocyanin is the best-studied of several redox-active metabolites of the opportunistic pathogen Pseudomonas aeruginosa that is responsible for biofilm formation and virulence. Pyocyanin oxidase, which disrupts biofilm formation, represents a therapeutic lead for difficult bacterial infections.
3 Two distant catalytic sites are responsible for C2c2 RNase activities.
Authors Liu L, Li X, Wang J, Wang M, Chen P, Yin M, Li J, Sheng G, Wang Y.
Citation Cell. 2017 Jan 12;168(1-2):121-34.e12.
PDB codes 5WTJ
Equipment PILATUS3 @ SSRF BL 19U1
Summary C2c2 is a CRISPR nuclease with two RNase activities, cutting its RNA target and processing CRISPR RNA. The crystal structure provides insight into the mechanism of the two RNase activities and establishes a framework for engineering of C2c2 as an RNA editing tool.
2 A supramolecular assembly mediates lentiviral DNA integration.
Authors Ballandras-Colas A, Maskell DP, Serrao E, Locke J, Swuec P, Jónsson SR, Kotecha A, Cook NJ, Pye VE, Taylor IA, Andrésdóttir V, Engelman AN, Costa A, Cherepanov P.
Citation Science. 2017 Jan 6;355(6320):93-5.
PDB codes 5LLJ 5T3A
Equipment PILATUS 6M @ DLS BL I04; PILATUS 2M @ DLS BL I04-1
Summary Lentiviruses like HIV-1 integrate their DNA into the host genome. Viral integrase is thus a major drug target. Using electron cryomicroscopy and X-ray crystallography, this study shows how integrase binds viral DNA to form a complex called the intasome that contains 16 integrase molecules in eight distinct conformations.
1 Structural basis of an essential interaction between influenza polymerase and Pol II CTD.
Authors Lukarska M, Fournier G, Pflug A, Resa-Infante P, Reich S, Naffakh N, Cusack S.
Citation Nature. 2017 Jan 5;541(7635):117-21.
PDB codes 5M3H 5M3J
Equipment PILATUS 6M @ ESRF BLs ID23-1, ID29
Summary Influenze polymerase is a heterotrimer that binds to promoters of each of the eight viral genome segments and performs transcription and replication. The crystal structure of bat influenza A polymerase bound to a peptide mimic of host RNA polymerase II C-terminal domain shows the fine-tuning required for efficient viral transcription and identifies targets for potential antiviral drugs.