Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120

被引：287

作者：

Kong, Leopold ^{[1
,2
]}

Lee, Jeong Hyun ^{[1
]}

Doores, Katie J. ^{[2
,3
,4
,5
]}

Murin, Charles D. ^{[1
]}

Julien, Jean-Philippe ^{[1
,2
]}

McBride, Ryan ^{[6
]}

Liu, Yan ^{[7
]}

Marozsan, Andre ^{[8
]}

Cupo, Albert ^{[8
]}

Klasse, Per-Johan ^{[8
]}

Hoffenberg, Simon ^{[9
]}

Caulfield, Michael ^{[9
]}

King, C. Richter ^{[9
]}

Hua, Yuanzi ^{[1
,2
]}

Le, Khoa M. ^{[2
,3
]}

Khayat, Reza ^{[1
]}

Deller, Marc C. ^{[1
,10
]}

Clayton, Thomas ^{[1
,10
]}

Tien, Henry ^{[1
,10
]}

Feizi, Ten ^{[7
]}

Sanders, Rogier W. ^{[8
,11
]}

Paulson, James C. ^{[6
]}

Moore, John P. ^{[8
]}

Stanfield, Robyn L. ^{[1
,2
]}

Burton, Dennis R. ^{[2
,3
,4
,5
,12
]}

Ward, Andrew B. ^{[1
,2
,12
]}

Wilson, Ian A. ^{[1
,2
,12
,13
]}

机构：

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

[2] Scripps Res Inst, Int AIDS Vaccine Initiat, Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[4] Massachusetts Gen Hosp, Ragon Inst, MIT, Cambridge, MA USA

[5] Harvard Univ, Cambridge, MA 02138 USA

[6] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA

[7] Univ London Imperial Coll Sci Technol & Med, Dept Med, Glycosci Lab, London, England

[8] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[9] Int AIDS Vaccine Initiat, Design & Dev Lab, Brooklyn, NY USA

[10] Scripps Res Inst, Joint Ctr Struct Genom, La Jolla, CA 92037 USA

[11] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[12] Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA

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

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2013年 / 20卷 / 07期

基金：

美国国家卫生研究院; 英国工程与自然科学研究理事会; 英国惠康基金;

关键词：

NEUTRALIZING ANTIBODIES; STRUCTURAL BASIS; POTENT; BROAD; EPITOPE; SITE; RECOGNITION; EVOLUTION; COMPLEX; DOMAIN;

D O I：

10.1038/nsmb.2594

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A substantial proportion of the broadly neutralizing antibodies (bnAbs) identified in certain HIV-infected donors recognize glycan-dependent epitopes on HIV-1 gp120. Here we elucidate how the bnAb PGT 135 binds its Asn332 glycan-dependent epitope from its 3.1-angstrom crystal structure with gp120, CD4 and Fab 17b. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield and access the gp120 protein surface. EM reveals that PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. Combined structural studies of PGT 135, PGT 128 and 2G12 show that this Asn332-dependent antigenic region is highly accessible and much more extensive than initially appreciated, which allows for multiple binding modes and varied angles of approach; thereby it represents a supersite of vulnerability for antibody neutralization.

引用

页码：796 / +

页数：10

共 46 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] Computation-Guided Backbone Grafting of a Discontinuous Motif onto a Protein Scaffold [J].

Azoitei, Mihai L. ;

Correia, Bruno E. ;

Ban, Yih-En Andrew ;

Carrico, Chris ;

Kalyuzhniy, Oleksandr ;

Chen, Lei ;

Schroeter, Alexandria ;

Huang, Po-Ssu ;

McLellan, Jason S. ;

Kwong, Peter D. ;

Baker, David ;

Strong, Roland K. ;

Schief, William R. .

SCIENCE, 2011, 334 (6054) :373-376

[3] Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization [J].

Binley, James M. ;

Ban, Yih-En Andrew ;

Crooks, Emma T. ;

Eggink, Dirk ;

Osawa, Keiko ;

Schief, William R. ;

Sanders, Rogier W. .

JOURNAL OF VIROLOGY, 2010, 84 (11) :5637-5655

[4] A Blueprint for HIV Vaccine Discovery [J].

Burton, Dennis R. ;

Ahmed, Rafi ;

Barouch, Dan H. ;

Butera, Salvatore T. ;

Crotty, Shane ;

Godzik, Adam ;

Kaufmann, Daniel E. ;

McElrath, M. Juliana ;

Nussenzweig, Michel C. ;

Pulendran, Bali ;

Scanlan, Chris N. ;

Schief, William R. ;

Silvestri, Guido ;

Streeck, Hendrik ;

Walker, Bruce D. ;

Walker, Laura M. ;

Ward, Andrew B. ;

Wilson, Ian A. ;

Wyatt, Richard .

CELL HOST & MICROBE, 2012, 12 (04) :396-407

[5]

Burton DR, 2001, CURR TOP MICROBIOL, V260, P109

[6] Antibody domain exchange is an immunological solution to carbohydrate cluster recognition [J].

Calarese, DA ;

Scanlan, CN ;

Zwick, MB ;

Deechongkit, S ;

Mimura, Y ;

Kunert, R ;

Zhu, P ;

Wormald, MR ;

Stanfield, RL ;

Roux, KH ;

Kelly, JW ;

Rudd, PM ;

Dwek, RA ;

Katinger, H ;

Burton, DR ;

Wilson, IA .

SCIENCE, 2003, 300 (5628) :2065-2071

[7] Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120 [J].

Chen, Lei ;

Kwon, Young Do ;

Zhou, Tongqing ;

Wu, Xueling ;

O'Dell, Sijy ;

Cavacini, Lisa ;

Hessell, Ann J. ;

Pancera, Marie ;

Tang, Min ;

Xu, Ling ;

Yang, Zhi-Yong ;

Zhang, Mei-Yun ;

Arthos, James ;

Burton, Dennis R. ;

Dimitrov, Dimiter S. ;

Nabel, Gary J. ;

Posner, Marshall R. ;

Sodroski, Joseph ;

Wyatt, Richard ;

Mascola, John R. ;

Kwong, Peter D. .

SCIENCE, 2009, 326 (5956) :1123-1127

[8] Polysaccharide mimicry of the epitope of the broadly neutralizing anti-HIV antibody, 2G12, induces enhanced antibody responses to self oligomannose glycans [J].

Dunlop, D. Cameron ;

Bonomelli, Camille ;

Mansab, Fatma ;

Vasiljevic, Snezana ;

Doores, Katie J. ;

Wormald, Mark R. ;

Palma, Angelina S. ;

Feizi, Ten ;

Harvey, David J. ;

Dwek, Raymond A. ;

Crispin, Max ;

Scanlan, Christopher N. .

GLYCOBIOLOGY, 2010, 20 (07) :812-823

[9] THE ALPHA-GLUCOSIDASE INHIBITOR N-BUTYLDEOXYNOJIRIMYCIN INHIBITS HUMAN-IMMUNODEFICIENCY-VIRUS ENTRY AT THE LEVEL OF POST-CD4-BINDING [J].

FISCHER, P ;

COLLIN, M ;

KARLSSON, GB ;

JAMES, W ;

BUTTERS, TD ;

DAVIS, SJ ;

GORDON, S ;

DWEK, RA ;

PLATT, FM .

JOURNAL OF VIROLOGY, 1995, 69 (09) :5791-5797

[10] The Neutralization Breadth of HIV-1 Develops Incrementally over Four Years and Is Associated with CD4+ T Cell Decline and High Viral Load during Acute Infection [J].

Gray, Elin S. ;

Madiga, Maphuti C. ;

Hermanus, Tandile ;

Moore, Penny L. ;

Wibmer, Constantinos Kurt ;

Tumba, Nancy L. ;

Werner, Lise ;

Mlisana, Koleka ;

Sibeko, Sengeziwe ;

Williamson, Carolyn ;

Karim, Salim S. Abdool ;

Morris, Lynn .

JOURNAL OF VIROLOGY, 2011, 85 (10) :4828-4840

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