Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16

被引：231

作者：

Pancera, Marie ^{[1
]}

Shahzad-ul-Hussan, Syed ^{[2
]}

Doria-Rose, Nicole A. ^{[1
]}

McLellan, Jason S. ^{[1
]}

Bailer, Robert T. ^{[1
]}

Dai, Kaifan ^{[1
]}

Loesgen, Sandra ^{[2
]}

Louder, Mark K. ^{[1
]}

Staupe, Ryan P. ^{[1
]}

Yang, Yongping ^{[1
]}

Zhang, Baoshan ^{[1
]}

Parks, Robert ^{[3
]}

Eudailey, Joshua ^{[3
]}

Lloyd, Krissey E. ^{[3
]}

Blinn, Julie ^{[3
]}

Alam, S. Munir ^{[3
]}

Haynes, Barton F. ^{[3
]}

Amin, Mohammed N. ^{[4
,5
]}

Wang, Lai-Xi ^{[4
,5
]}

Burton, Dennis R. ^{[6
,7
,8
,9
,10
]}

Koff, Wayne C. ^{[11
]}

Nabel, Gary J. ^{[1
]}

Mascola, John R. ^{[1
]}

Bewley, Carole A. ^{[2
]}

Kwong, Peter D. ^{[1
]}

机构：

[1] NIAID, Vaccine Res Ctr, US Natl Inst Hlth, Bethesda, MD 20892 USA

[2] NIDDK, Lab Bioorgan Chem, US Natl Inst Hlth, Bethesda, MD 20892 USA

[3] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA

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

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

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

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

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

[9] Harvard Univ, Cambridge, MA 02138 USA

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

[11] Int AIDS Vaccine Initiat, New York, NY USA

来源：

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

基金：

美国国家卫生研究院;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; BROADLY NEUTRALIZING ANTIBODIES; HIV-1 ENVELOPE GLYCOPROTEINS; HAMSTER OVARY CELLS; GLYCOSYLATION SITES; CRYSTAL-STRUCTURE; 2G12; RECOGNIZES; GP120; POTENT; COMPLEX;

D O I：

10.1038/nsmb.2600

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：

HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1-V2, showing an epitope comprising both high mannose-type and complex-type N-linked glycans. We combined structure, NMR and mutagenesis analyses to characterize glycan recognition by PG9 and PG16. Three PG16-specific residues, arginine, serine and histidine (RSH), were critical for binding sialic acid on complex-type glycans, and introduction of these residues into PG9 produced a chimeric antibody with enhanced HIV-1 neutralization. Although HIV-1-glycan diversity facilitates evasion, antibody somatic diversity can overcome this and can provide clues to guide the design of modified antibodies with enhanced neutralization.

引用

页码：804 / +

页数：11

共 62 条

[51] Broad neutralization coverage of HIV by multiple highly potent antibodies [J].

Walker, Laura M. ;

Huber, Michael ;

Doores, Katie J. ;

Falkowska, Emilia ;

Pejchal, Robert ;

Julien, Jean-Philippe ;

Wang, Sheng-Kai ;

Ramos, Alejandra ;

Chan-Hui, Po-Ying ;

Moyle, Matthew ;

Mitcham, Jennifer L. ;

Hammond, Phillip W. ;

Olsen, Ole A. ;

Pham Phung ;

Fling, Steven ;

Wong, Chi-Huey ;

Phogat, Sanjay ;

Wrin, Terri ;

Simek, Melissa D. ;

Koff, Wayne C. ;

Wilson, Ian A. ;

Burton, Dennis R. ;

Poignard, Pascal .

NATURE, 2011, 477 (7365) :466-U117

[52] A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals [J].

Walker, Laura M. ;

Simek, Melissa D. ;

Priddy, Frances ;

Gach, Johannes S. ;

Wagner, Denise ;

Zwick, Michael B. ;

Phogat, Sanjay K. ;

Poignard, Pascal ;

Burton, Dennis R. .

PLOS PATHOGENS, 2010, 6 (08) :11-12

[53] Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target [J].

Walker, Laura M. ;

Phogat, Sanjay K. ;

Chan-Hui, Po-Ying ;

Wagner, Denise ;

Phung, Pham ;

Goss, Julie L. ;

Wrin, Terri ;

Simek, Melissa D. ;

Fling, Steven ;

Mitcham, Jennifer L. ;

Lehrman, Jennifer K. ;

Priddy, Frances H. ;

Olsen, Ole A. ;

Frey, Steven M. ;

Hammond, Phillip W. ;

Kaminsky, Stephen ;

Zamb, Timothy ;

Moyle, Matthew ;

Koff, Wayne C. ;

Poignard, Pascal ;

Burton, Dennis R. .

SCIENCE, 2009, 326 (5950) :285-289

[54] Binding of high-mannose-type oligosaccharides and synthetic oligomannose clusters to human antibody 2G12: Implications for HIV-1 vaccine design [J].

Wang, LX ;

Ni, JH ;

Singh, S ;

Li, HG .

CHEMISTRY & BIOLOGY, 2004, 11 (01) :127-134

[55] Antibody neutralization and escape by HIV-1 [J].

Wei, XP ;

Decker, JM ;

Wang, SY ;

Hui, HX ;

Kappes, JC ;

Wu, XY ;

Salazar-Gonzalez, JF ;

Salazar, MG ;

Kilby, JM ;

Saag, MS ;

Komarova, NL ;

Nowak, MA ;

Hahn, BH ;

Kwong, PD ;

Shaw, GM .

NATURE, 2003, 422 (6929) :307-312

[56] Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing [J].

Wu, Xueling ;

Zhou, Tongqing ;

Zhu, Jiang ;

Zhang, Baoshan ;

Georgiev, Ivelin ;

Wang, Charlene ;

Chen, Xuejun ;

Longo, Nancy S. ;

Louder, Mark ;

McKee, Krisha ;

O'Dell, Sijy ;

Perfetto, Stephen ;

Schmidt, Stephen D. ;

Shi, Wei ;

Wu, Lan ;

Yang, Yongping ;

Yang, Zhi-Yong ;

Yang, Zhongjia ;

Zhang, Zhenhai ;

Bonsignori, Mattia ;

Crump, John A. ;

Kapiga, Saidi H. ;

Sam, Noel E. ;

Haynes, Barton F. ;

Simek, Melissa ;

Burton, Dennis R. ;

Koff, Wayne C. ;

Doria-Rose, Nicole A. ;

Connors, Mark ;

Mullikin, James C. ;

Nabel, Gary J. ;

Roederer, Mario ;

Shapiro, Lawrence ;

Kwong, Peter D. ;

Mascola, John R. .

SCIENCE, 2011, 333 (6049) :1593-1602

[57] Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1 [J].

Wu, Xueling ;

Yang, Zhi-Yong ;

Li, Yuxing ;

Hogerkorp, Carl-Magnus ;

Schief, William R. ;

Seaman, Michael S. ;

Zhou, Tongqing ;

Schmidt, Stephen D. ;

Wu, Lan ;

Xu, Ling ;

Longo, Nancy S. ;

McKee, Krisha ;

O'Dell, Sijy ;

Louder, Mark K. ;

Wycuff, Diane L. ;

Feng, Yu ;

Nason, Martha ;

Doria-Rose, Nicole ;

Connors, Mark ;

Kwong, Peter D. ;

Roederer, Mario ;

Wyatt, Richard T. ;

Nabel, Gary J. ;

Mascola, John R. .

SCIENCE, 2010, 329 (5993) :856-861

[58] The antigenic structure of the HIV gp120 envelope glycoprotein [J].

Wyatt, R ;

Kwong, PD ;

Desjardins, E ;

Sweet, RW ;

Robinson, J ;

Hendrickson, WA ;

Sodroski, JG .

NATURE, 1998, 393 (6686) :705-711

[59] The HIV-1 envelope glycoproteins: Fusogens, antigens, and immunogens [J].

Wyatt, R ;

Sodroski, J .

SCIENCE, 1998, 280 (5371) :1884-1888

[60] Somatic populations of PGT135-137 HIV-1-neutralizing antibodies identified by 454 pyrosequencing and bioinfornnatics [J].

Zhu, Jiang ;

O'Dell, Sijy ;

Ofek, Gilad ;

Pancera, Marie ;

Wu, Xueling ;

Zhang, Baoshan ;

Zhang, Zhenhai ;

Mullikin, James C. ;

Simek, Melissa ;

Burton, Dennis R. ;

Koff, Wayne C. ;

Shapiro, Lawrence ;

Mascola, John R. ;

Kwong, Peter D. .

FRONTIERS IN MICROBIOLOGY, 2012, 3

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