上海光源生物大分子晶体学线站用户高水平产出再创佳绩
近日，上海光源生物大分子晶体学线站BL02U1（原BL17U1）用户发表的CNS（Cell/Nature/Science）论文数量突破100篇。其中包括中国科学十大进展4项、中国生命科学十大进展2项、中国医学十大进展1项、国家自然科学奖二等奖1项。自2010年用户发表第一篇Nature以来，用户解析的蛋白质结构数不断创造新高，从2011年到2020年连续十年该线站发表的论文总数和RCR(Relative Citation Ratio)在全球130多条生物大分子晶体学线站中排名第一。
上海光源生物大分子晶体学线站(原BL17U1)是我国首条基于第三代同步辐射光源的生物大分子晶体学线站。自2009年建成以来，线站一直高效运行，在满足用户需求的同时，不断开展技术能力提升。最初阶段，线站只配备了MarDTB和Mar225 CCD探测器，用户需手动上样。2011年在中国科学院运行维修改造项目的支持下进行了第一次升级，采用ADSC Q315 CCD探测器、高精度衍射仪和自动上样机械手，成功移植Blu-Ice软件实现系统集成，并提供了用户友好的界面。2017年多渠道支持下进行了第二次升级，自主研发高精度衍射仪，并将探测器升级为EIGER X 16M，为匹配高速数据采集开发了数据自动处理系统Aquarium。2021年，为支持上海光源线站工程中的高性能膜蛋白线站建设，该线站从BL17U1搬迁至BL02U1，进一步通过光束线设计的优化升级，实现了高亮度的微小光斑，自主研发的上样机械手Swordfish，极大提高了上样速度，从而进一步提高实验效率。自主开发的数据采集系统Finback整合了各项实验设备，提供gridscan和helix等数据采集方式，并实现远程实验开放。
通过持续的平台升级和技术创新，上海光源生物大分子晶体学线站为用户提供高效先进技术平台，有力地支持了我国结构生物学研究的快速发展。
线站能力升级获以下项目支持：
1.国家重点研发项目,国家重点研发项目，2017YFA0504901,微小晶体高效结构测定技术研究
2.国家重大科学研究计划项目，973项目，2011CB911102，基于细聚焦同步辐射光束线站的微小晶体结构测定技术的研究和应用
3.中国科学院战略性先导科技专项（B类），XDB08030101，同步辐射X射线细聚焦技术及应用
4.中国科学院2009维修改造项目“生物大分子晶体衍射高分辨结构测定和自动化筛选系统项目”
图1：使用BL02U1/BL17U1发表在CNS上的部分蛋白结构
图2：2011年-2020年全球生物大分子晶体学线站发表论文总数和RCR排名
论文数据来源：http://biosync.sbkb.org；
RCR数据来源：https://icite.od.nih.gov, doi: 10.1371/journal.pbio.1002541
用户发表的100篇CNS论文列表：
1 Crystal Structure of the Caenorhabditis elegans Apoptosome Reveals an Octameric Assembly of CED-4. Cell, 2010
2 Structure of a fucose transporter in an outward-open conformation. Nature, 2010
3 Structural basis for site-specific ribose methylation by box C/D RNA protein complexes. Nature, 2011
4 Structural insight into brassinosteroid perception by BRI1. Nature, 2011
5 Structure of MyTH4-FERM Domains in Myosin VIIa Tail Bound to Cargo. Science, 2011
6 Structure and mechanism of the hexameric MecA–ClpC molecular machine. Nature, 2011
7 Structure and mechanism of the uracil transporter UraA. Nature, 2011
8 Structural insight into the type-II mitochondrial NADH dehydrogenases. Nature, 2012
9 Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature, 2012
10 Structure and mechanism of a glutamate–GABA antiporter. Nature, 2012
11 Structural basis of ultraviolet-B perception by UVR8. Nature, 2012
12 Crystal structure of a bacterial homologue of glucose transporters GLUT1–4. Nature, 2012
13 Structural Basis for Sequence-Specific Recognition of DNA by TAL Effectors. Science, 2012
14 Chitin-Induced Dimerization Activates a Plant Immune Receptor. Science, 2012
15 Crystal Structure of TET2-DNA Complex: Insight into TET-Mediated 5mC Oxidation. Cell, 2013
16 Structural basis for the modular recognition of single-stranded RNA by PPR proteins. Nature, 2013
17 Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature, 2013
18 Structure of a bacterial energy-coupling factor transporter. Nature, 2013
19 Crystal structure of a folate energy-coupling factor transporter from Lactobacillus brevis. Nature, 2013
20 SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature, 2013
21 Structure of a presenilin family intramembrane aspartate protease. Nature, 2013
22 Crystal Structure of NLRC4 Reveals Its Autoinhibition Mechanism. Science, 2013
23 FtsZ Protofilaments Use a Hinge-Opening Mechanism for Constrictive Force Generation. Science, 2013
24 Structural basis for flg22-induced activation of the Arabidopsis FLS2-BAK1 immune complex. Science, 2013
25 Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses. Science, 2013
26 Conserved regulatory elements in AMPK. Nature, 2013
27 An Airborne Transmissible Avian Influenza H5 Hemagglutinin Seen at the Atomic Level. Science, 2013
28 AF9 YEATS Domain Links Histone Acetylation to DOT1L-Mediated H3K79 Methylation. Cell, 2014
29 Molecular Mechanism of Action of Plant DRM De Novo DNA Methyltransferases. Cell, 2014
30 Crystal structures of the Lsm complex bound to the 3′ end sequence of U6 small nuclear RNA. Nature, 2014
31 Crystal structure of the RNA-guided immune surveillance Cascade complex in Escherichia coli. Nature, 2014
32 Crystal structure of the human glucose transporter GLUT1. Nature, 2014
33 ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression. Nature, 2014
34 Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif. Nature, 2014
35 Structural basis for lipopolysaccharide insertion in the bacterial outer. Nature, 2014
36 Allosteric receptor activation by the plant peptide hormone phytosulfokine. Nature, 2015
37 Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids. Cell, 2015
38 Structural insight into substrate preference for TET-mediated oxidation. Nature, 2015
39 Architecture of the mammalian mechanosensitive Piezo1 channel. Nature, 2015
40 Molecular basis of ligand recognition and transport by glucose transporters. Nature, 2015
41 Structural insight into autoinhibition and histone H3-induced activation of DNMT3A. Nature, 2015
42 Structural and Mechanistic Basis of PAM-Dependent Spacer Acquisition in CRISPR-Cas Systems. Cell, 2015
43 Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels. Science, 2015
44 Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1. Cell, 2016
45 The crystal structure of Cpf1 in complex with CRISPR RNA. Nature, 2016
46 Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex. Nature, 2016
47 The bacteriophage ？29 tail possesses a pore-forming loop for cell membrane penetration. Nature, 2016
48 Structural basis for activity regulation of MLL family methyltransferases. Nature, 2016
49 DWARF14 is a non-canonical hormone receptor for strigolactone. Nature, 2016
50 Phase Transition in Postsynaptic Densities Underlies Formation of Synaptic Complexes and Synaptic Plasticity. Cell, 2016
51 Crystal Structure of the Human Cannabinoid Receptor CB1. Cell, 2016
52 Pore architecture of TRIC channels and insights into their gating mechanism. Nature, 2016
53 Structure and regulation of the chromatin remodeller ISWI. Nature, 2016
54 Structural basis of CRISPR-SpyCas9 inhibition by an anti-CRISPR protein. Nature, 2017
55 Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators. Nature, 2017
56 ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia. Nature, 2017
57 Two Distant Catalytic Sites Are Responsible for C2c2 RNase Activities. Cell, 2017
58 MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion. Nature, 2017
59 The Molecular Architecture for RNA-Guided RNA Cleavage by Cas13a. Cell, 2017
60 Polycomb-like proteins link the PRC2 complex to CpG islands. Nature, 2017
61 Multisite Substrate Recognition in Asf1-Dependent Acetylation of Histone H3 K56 by Rtt109. Cell, 2018
62 Structural basis of ubiquitin modification by theLegionella effector SdeA. Nature, 2018
63 Structural Insights into Non-canonical Ubiquitination Catalyzed by SidE. Cell, 2018
64 "Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference. Cell, 2018 "
65 Single-crystal X-ray diffraction structures of covalent organic frameworks. Science, 2018
66 Molecular Basis of Arthritogenic Alphavirus Receptor MXRA8 Binding to Chikungunya Virus Envelope Protein. Cell, 2019
67 Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target. Cell, 2019
68 Enzyme-catalysed [6+4] cycloadditions in the biosynthesis of natural products. Nature, 2019
69 Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase. Nature, 2019
70 Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds. Nature, 2019
71 Structural basis for enzymatic photocatalysis in chlorophyll biosynthesis. Nature, 2019
72 Mechanisms of RALF peptide perception by a heterotypic receptor complex. Nature, 2019
73 Structural basis for blue-green light harvesting and energy dissipation in diatoms. Science, 2019
74 Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, 2020
75 Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell, 2020
76 A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Science, 2020
77 Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science, 2020
78 Structure of Mprofrom SARS-CoV-2 and discovery of its inhibitors. Nature, 2020
79 Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature, 2020
80 A human neutralizing antibody targets the receptor binding site of SARS-CoV-2. Nature, 2020
81 A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS. Cell, 2020
82 Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy. Cell, 2020
83 An enzymatic Alder-ene reaction. Nature, 2020
84 Structural Mechanism for GSDMD Targeting by Autoprocessed Caspases in Pyroptosis. Cell, 2020
85 Histone H3.3 phosphorylation amplifies stimulation-induced transcription. Nature, 2020
86 Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol. Science, 2020
87 A broadly protective antibody that targets the flavivirus NS1 protein. Science, 2021
88 Structural and biochemical mechanisms of NLRP1 inhibition by DPP9. Nature, 2021
89 Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species. Cell, 2021
90 Highly enriched BEND3 prevents the premature activation of bivalent genes during differentiation. Science, 2022
91 Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity. Science, 2022
92 A backbone-centred energy function of neural networks for protein design. Nature, 2022
93 Crucial role and mechanism of transcription-coupled DNA repair in bacteria. Nature, 2022
94 Enantioselective [2+2]-cycloadditions with triplet photoenzymes. Nature, 2022
95 Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1. Cell, 2022
96 Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2. Cell, 2022
97 The Parallel Presentation of Two Functional CTL Epitopes Derived from the O and Asia 1 Serotypes of Foot-and-Mouth Disease Virus and Swine SLA-2*HB01: Implications for Universal Vaccine Development. Cell, 2023
98 Bacteriophages inhibit and evade cGAS-like immune function in bacteria. Cell, 2023
99 De novo design of protein interactions with learned surface fingerprints. Nature, 2023
100 Pathogen protein modularity enables elaboratemimicry of a host phosphatase. Cell, 2023
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