Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies

被引：4

作者：

Cottrell, Christopher A. ^{[1
]}

Manne, Kartik ^{[2
,3
,4
]}

Kong, Rui ^{[5
]}

Wang, Shuishu ^{[5
]}

Zhou, Tongqing ^{[5
]}

Chuang, Gwo-Yu ^{[5
]}

Edwards, Robert J. ^{[2
,3
,4
]}

Henderson, Rory ^{[2
,3
,4
]}

Janowska, Katarzyna ^{[2
,3
,4
]}

Kopp, Megan ^{[2
,3
,4
]}

Lin, Bob C. ^{[5
]}

Louder, Mark K. ^{[5
]}

Olia, Adam S. ^{[5
]}

Rawi, Reda ^{[5
]}

Shen, Chen-Hsiang ^{[5
]}

Taft, Justin D. ^{[5
]}

Torres, Jonathan L. ^{[1
]}

Wu, Nelson R. ^{[1
]}

Zhang, Baoshan ^{[5
]}

Doria-Rose, Nicole A. ^{[5
]}

Cohen, Myron S. ^{[6
,7
,8
]}

Haynes, Barton F. ^{[2
,3
]}

Shapiro, Lawrence ^{[5
]}

Ward, Andrew B. ^{[1
]}

Acharya, Priyamvada ^{[2
,3
,4
,5
]}

Mascola, John R. ^{[5
]}

Kwong, Peter D. ^{[5
,9
]}

机构：

[1] Scripps Res Inst, Dept Integrat Struct & Computat Biol, Consortium HIV AIDS Vaccine Dev CHAVD, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

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

[3] Duke Univ, Sch Med, Human Vaccine Inst, Dept Surg, Durham, NC 27710 USA

[4] Duke Univ, Ctr HIV AIDS Vaccine Immunol Immunogen Discovery, Durham, NC 27710 USA

[5] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[6] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA

[7] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA

[8] Univ N Carolina, Dept Microbiol, Chapel Hill, NC 27599 USA

[9] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA

来源：

CELL REPORTS | 2021年 / 37卷 / 05期

基金：

美国国家科学基金会;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; N-LINKED GLYCAN; HIV-1-NEUTRALIZING ANTIBODIES; MATURATION PATHWAY; GERMLINE; REVEALS; MODEL; SITE; BINDING; IDENTIFICATION;

D O I：

10.1016/j.celrep.2021.109922

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition.

引用

页数：20

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