An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain

被引：76

作者：

Wu, Nicholas C. ^{[1
,2
]}

Yuan, Meng ^{[3
]}

Liu, Hejun ^{[3
]}

Lee, Chang-Chun D. ^{[3
]}

Zhu, Xueyong ^{[3
]}

Bangaru, Sandhya ^{[3
]}

Torres, Jonathan L. ^{[3
]}

Caniels, Tom G. ^{[4
]}

Brouwer, Philip J. M. ^{[4
]}

van Gils, Marit J. ^{[4
]}

Sanders, Rogier W. ^{[4
,5
]}

Ward, Andrew B. ^{[3
,6
,7
]}

Wilson, Ian A. ^{[3
,6
,7
,8
]}

机构：

[1] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA

[2] Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA

[3] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[4] Univ Amsterdam, Amsterdam Infect & Immun Inst, Dept Med Microbiol, Amsterdam UMC, NL-1105 AZ Amsterdam, Netherlands

[5] Cornell Univ, Dept Microbiol & Immunol, Weill Med Coll, New York, NY 10021 USA

[6] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[7] Scripps Res Inst, Consortium HIV AIDS Vaccine Dev CHAVD, La Jolla, CA 92037 USA

[8] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

CELL REPORTS | 2020年 / 33卷 / 03期

关键词：

POTENT NEUTRALIZING ANTIBODIES;

D O I：

10.1016/j.celrep.2020.108274

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

IGHV3-53-encoded neutralizing antibodies are commonly elicited during SARS-CoV-2 infection and target the receptor-binding domain (RBD) of the spike (S) protein. Such IGHV3-53 antibodies generally have a short CDR H3 because of structural constraints in binding the RBD (mode A). However, a small subset of IGHV3-53 antibodies to the RBD contain a longer CDR H3. Crystal structures of two IGHV3-53 neutralizing antibodies here demonstrate that a longer CDR H3 can be accommodated in a different binding mode (mode B). These two classes of IGHV3-53 antibodies both target the ACE2 receptor binding site, but with very different angles of approach and molecular interactions. Overall, these findings emphasize the versatility of IGHV3-53 in this common anti- body response to SARS-CoV-2, where conserved IGHV3-53 germline-encoded features can be combined with very different CDR H3 lengths and light chains for SARS-CoV-2 RBD recognition and virus neutralization.

引用

页数：11

共 35 条

[1] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].

Adams, Paul D. ;

Afonine, Pavel V. ;

Bunkoczi, Gabor ;

Chen, Vincent B. ;

Davis, Ian W. ;

Echols, Nathaniel ;

Headd, Jeffrey J. ;

Hung, Li-Wei ;

Kapral, Gary J. ;

Grosse-Kunstleve, Ralf W. ;

McCoy, Airlie J. ;

Moriarty, Nigel W. ;

Oeffner, Robert ;

Read, Randy J. ;

Richardson, David C. ;

Richardson, Jane S. ;

Terwilliger, Thomas C. ;

Zwart, Peter H. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :213-221

[2]

[Anonymous], 2020, CELL, DOI DOI 10.1016/j.cell.2020.06.025

[3]

Barnes Christopher O, 2020, bioRxiv, DOI 10.1101/2020.08.30.273920

[4] Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability [J].

Brouwer, Philip J. M. ;

Caniels, Tom G. ;

van der Straten, Karlijn ;

Snitselaar, Jonne L. ;

Aldon, Yoann ;

Bangaru, Sandhya ;

Torres, Jonathan L. ;

Okba, Nisreen M. A. ;

Claireaux, Mathieu ;

Kerster, Gius ;

Bentlage, Arthur E. H. ;

van Haaren, Marlies M. ;

Guerra, Denise ;

Burger, Judith A. ;

Schermer, Edith E. ;

Verheul, Kirsten D. ;

van der Velde, Niels ;

van der Kooi, Alex ;

van Schooten, Jelle ;

van Breemen, Marielle J. ;

Bijl, Tom P. L. ;

Sliepen, Kwinten ;

Aartse, Aafke ;

Derking, Ronald ;

Bontjer, Ilja ;

Kootstra, Neeltje A. ;

Wiersinga, W. Joost ;

Vidarsson, Gestur ;

Haagmans, Bart L. ;

Ward, Andrew B. ;

de Bree, Godelieve J. ;

Sanders, Rogier W. ;

van Gils, Marit J. .

SCIENCE, 2020, 369 (6504) :643-+

[5] Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells [J].

Cao, Yunlong ;

Su, Bin ;

Guo, Xianghua ;

Sun, Wenjie ;

Deng, Yongqiang ;

Bao, Linlin ;

Zhu, Qinyu ;

Zhang, Xu ;

Zheng, Yinghui ;

Geng, Chenyang ;

Chai, Xiaoran ;

He, Runsheng ;

Li, Xiaofeng ;

Lv, Qi ;

Zhu, Hua ;

Deng, Wei ;

Xu, Yanfeng ;

Wang, Yanjun ;

Qiao, Luxin ;

Tan, Yafang ;

Song, Liyang ;

Wang, Guopeng ;

Du, Xiaoxia ;

Gao, Ning ;

Liu, Jiangning ;

Xiao, Junyu ;

Su, Xiao-dong ;

Du, Zongmin ;

Feng, Yingmei ;

Qin, Chuan ;

Qin, Chengfeng ;

Jin, Ronghua ;

Xie, X. Sunney .

CELL, 2020, 182 (01) :73-+

[6] MolProbity: all-atom structure validation for macromolecular crystallography [J].

Chen, Vincent B. ;

Arendall, W. Bryan, III ;

Headd, Jeffrey J. ;

Keedy, Daniel A. ;

Immormino, Robert M. ;

Kapral, Gary J. ;

Murray, Laura W. ;

Richardson, Jane S. ;

Richardson, David C. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :12-21

[7] A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2 [J].

Chi, Xiangyang ;

Yan, Renhong ;

Zhang, Jun ;

Zhang, Guanying ;

Zhang, Yuanyuan ;

Hao, Meng ;

Zhang, Zhe ;

Fan, Pengfei ;

Dong, Yunzhu ;

Yang, Yilong ;

Chen, Zhengshan ;

Guo, Yingying ;

Zhang, Jinlong ;

Li, Yaning ;

Song, Xiaohong ;

Chen, Yi ;

Xia, Lu ;

Fu, Ling ;

Hou, Lihua ;

Xu, Junjie ;

Yu, Changming ;

Li, Jianmin ;

Zhou, Qiang ;

Chen, Wei .

SCIENCE, 2020, 369 (6504) :650-+

[8] Cross-neutralization of influenza A viruses mediated by a single antibody loop [J].

Ekiert, Damian C. ;

Kashyap, Arun K. ;

Steel, John ;

Rubrum, Adam ;

Bhabha, Gira ;

Khayat, Reza ;

Lee, Jeong Hyun ;

Dillon, Michael A. ;

O'Neil, Ryann E. ;

Faynboym, Aleksandr M. ;

Horowitz, Michael ;

Horowitz, Lawrence ;

Ward, Andrew B. ;

Palese, Peter ;

Webby, Richard ;

Lerner, Richard A. ;

Bhatt, Ramesh R. ;

Wilson, Ian A. .

NATURE, 2012, 489 (7417) :526-+

[9] A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses [J].

Ekiert, Damian C. ;

Friesen, Robert H. E. ;

Bhabha, Gira ;

Kwaks, Ted ;

Jongeneelen, Mandy ;

Yu, Wenli ;

Ophorst, Carla ;

Cox, Freek ;

Korse, Hans J. W. M. ;

Brandenburg, Boerries ;

Vogels, Ronald ;

Brakenhoff, Just P. J. ;

Kompier, Ronald ;

Koldijk, Martin H. ;

Cornelissen, Lisette A. H. M. ;

Poon, Leo L. M. ;

Peiris, Malik ;

Koudstaal, Wouter ;

Wilson, Ian A. ;

Goudsmit, Jaap .

SCIENCE, 2011, 333 (6044) :843-850

[10] Features and development of Coot [J].

Emsley, P. ;

Lohkamp, B. ;

Scott, W. G. ;

Cowtan, K. .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2010, 66 :486-501

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