Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9

被引：693

作者：

McLellan, Jason S. ^{[1
]}

Pancera, Marie ^{[1
]}

Carrico, Chris ^{[2
]}

Gorman, Jason ^{[1
]}

Julien, Jean-Philippe ^{[3
,4
]}

Khayat, Reza ^{[3
,4
]}

Louder, Robert ^{[1
]}

Pejchal, Robert ^{[3
,4
]}

Sastry, Mallika ^{[1
]}

Dai, Kaifan ^{[1
]}

O'Dell, Sijy ^{[1
]}

Patel, Nikita ^{[5
]}

Shahzad-ul-Hussan, Syed ^{[1
,6
]}

Yang, Yongping ^{[1
]}

Zhang, Baoshan ^{[1
]}

Zhou, Tongqing ^{[1
]}

Zhu, Jiang ^{[1
]}

Boyington, Jeffrey C. ^{[1
]}

Chuang, Gwo-Yu ^{[1
]}

Diwanji, Devan ^{[3
,4
]}

Georgiev, Ivelin ^{[1
]}

Do Kwon, Young ^{[1
]}

Lee, Doyung ^{[1
]}

Louder, Mark K. ^{[1
]}

Moquin, Stephanie ^{[1
]}

Schmidt, Stephen D. ^{[1
]}

Yang, Zhi-Yong ^{[1
]}

Bonsignori, Mattia ^{[7
]}

Crump, John A. ^{[8
,9
,10
,11
]}

Kapiga, Saidi H. ^{[12
]}

Sam, Noel E. ^{[10
,11
,12
]}

Haynes, Barton F. ^{[7
]}

Burton, Dennis R. ^{[14
]}

Koff, Wayne C. ^{[15
]}

Walker, Laura M.

Phogat, Sanjay ^{[15
]}

Wyatt, Richard ^{[13
]}

Orwenyo, Jared ^{[16
,17
]}

Wang, Lai-Xi ^{[16
,17
]}

Arthos, James ^{[5
]}

Bewley, Carole A. ^{[6
]}

Mascola, John R. ^{[1
]}

Nabel, Gary J. ^{[1
]}

Schief, William R. ^{[2
]}

Ward, Andrew B. ^{[3
,4
]}

Wilson, Ian A. ^{[3
,4
]}

Kwong, Peter D. ^{[1
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[3] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

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

[5] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

[6] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA

[7] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA

[8] Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA

[9] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA

[10] Tumaini Univ, Kilimanjaro Christian Med Ctr, Moshi, Tanzania

[11] Tumaini Univ, Kilimanjaro Christian Med Coll, Moshi, Tanzania

[12] Kilimanjaro Reprod Hlth Programme, Moshi, Tanzania

[13] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, TSRI, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[14] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02129 USA

[15] IAVI, New York, NY 10004 USA

[16] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA

[17] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA

来源：

NATURE | 2011年 / 480卷 / 7377期

基金：

美国国家卫生研究院;

关键词：

ENVELOPE GLYCOPROTEINS; POTENT NEUTRALIZATION; DEXTRAN SULFATE; IMMUNODEFICIENCY; EPITOPE; SOFTWARE; BINDING; REGION; CRYSTALLIZATION; ARCHITECTURE;

D O I：

10.1038/nature10696

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded beta-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.

引用

页码：336 / U86

页数：10

共 69 条

[1] PHENIX:: building new software for automated crystallographic structure determination [J].

Adams, PD ;

Grosse-Kunstleve, RW ;

Hung, LW ;

Ioerger, TR ;

McCoy, AJ ;

Moriarty, NW ;

Read, RJ ;

Sacchettini, JC ;

Sauter, NK ;

Terwilliger, TC .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2002, 58 :1948-1954

[2]

[Anonymous], 2011, PYMOL MOL GRAPH SYST

[3] HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells [J].

Arthos, James ;

Cicala, Claudia ;

Martinelli, Elena ;

Macleod, Katilyn ;

Van Ryk, Donald ;

Wei, Danlan ;

Xiao, Zhen ;

Veenstra, Timothy D. ;

Conrad, Thomas P. ;

Lempicki, Richard A. ;

McLaughlin, Sherry ;

Pascuccio, Massimiliano ;

Gopaul, Ravindra ;

McNally, Jonathan ;

Cruz, Catherine C. ;

Censoplano, Nina ;

Chung, Eva ;

Reitano, Kristin N. ;

Kottilil, Shyam ;

Goode, Diana J. ;

Fauci, Anthony S. .

NATURE IMMUNOLOGY, 2008, 9 (03) :301-309

[4] 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

[5] Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors [J].

Bonsignori, Mattia ;

Hwang, Kwan-Ki ;

Chen, Xi ;

Tsao, Chun-Yen ;

Morris, Lynn ;

Gray, Elin ;

Marshall, Dawn J. ;

Crump, John A. ;

Kapiga, Saidi H. ;

Sam, Noel E. ;

Sinangil, Faruk ;

Pancera, Marie ;

Yang Yongping ;

Zhang, Baoshan ;

Zhu, Jiang ;

Kwong, Peter D. ;

O'Dell, Sijy ;

Mascola, John R. ;

Wu, Lan ;

Nabel, Gary J. ;

Phogat, Sanjay ;

Seaman, Michael S. ;

Whitesides, John F. ;

Moody, M. Anthony ;

Kelsoe, Garnett ;

Yang, Xinzhen ;

Sodroski, Joseph ;

Shaw, George M. ;

Montefiori, David C. ;

Kepler, Thomas B. ;

Tomaras, Georgia D. ;

Alam, S. Munir ;

Liao, Hua-Xin ;

Haynes, Barton F. .

JOURNAL OF VIROLOGY, 2011, 85 (19) :9998-10009

[6] Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].

Brunger, AT ;

Adams, PD ;

Clore, GM ;

DeLano, WL ;

Gros, P ;

Grosse-Kunstleve, RW ;

Jiang, JS ;

Kuszewski, J ;

Nilges, M ;

Pannu, NS ;

Read, RJ ;

Rice, LM ;

Simonson, T ;

Warren, GL .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921

[7] Replication and neutralization of human immunodeficiency virus type 1 lacking the V1 and V2 variable loops of the gp120 envelope glycoprotein [J].

Cao, J ;

Sullivan, N ;

Desjardin, E ;

Parolin, C ;

Robinson, J ;

Wyatt, R ;

Sodroski, J .

JOURNAL OF VIROLOGY, 1997, 71 (12) :9808-9812

[8] Three-dimensional structure of the Fab from a human IgM cold agglutinin [J].

Cauerhff, A ;

Braden, BC ;

Carvalho, JG ;

Aparicio, R ;

Polikarpov, I ;

Leoni, J ;

Goldbaum, FA .

JOURNAL OF IMMUNOLOGY, 2000, 165 (11) :6422-6428

[9] Crystal Structure of Human Antibody 2909 Reveals Conserved Features of Quaternary Structure-Specific Antibodies That Potently Neutralize HIV-1 [J].

Changela, Anita ;

Wu, Xueling ;

Yang, Yongping ;

Zhang, Baoshan ;

Zhu, Jiang ;

Nardone, Glenn A. ;

O'Dell, Sijy ;

Pancera, Marie ;

Gorny, Miroslaw K. ;

Phogat, Sanjay ;

Robinson, James E. ;

Stamatatos, Leonidas ;

Zolla-Pazner, Susan ;

Mascola, John R. ;

Kwong, Peter D. .

JOURNAL OF VIROLOGY, 2011, 85 (06) :2524-2535

[10] Structure of an unliganded simian immunodeficiency virus gp120 core [J].

Chen, B ;

Vogan, EM ;

Gong, HY ;

Skehel, JJ ;

Wiley, DC ;

Harrison, SC .

NATURE, 2005, 433 (7028) :834-841

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