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

Summary: 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-dep...

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Autores principales:	Christopher A. Cottrell, Kartik Manne, Rui Kong, Shuishu Wang, Tongqing Zhou, Gwo-Yu Chuang, Robert J. Edwards, Rory Henderson, Katarzyna Janowska, Megan Kopp, Bob C. Lin, Mark K. Louder, Adam S. Olia, Reda Rawi, Chen-Hsiang Shen, Justin D. Taft, Jonathan L. Torres, Nelson R. Wu, Baoshan Zhang, Nicole A. Doria-Rose, Myron S. Cohen, Barton F. Haynes, Lawrence Shapiro, Andrew B. Ward, Priyamvada Acharya, John R. Mascola, Peter D. Kwong
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	antibody-antigen binding antibody approach angle CD4 binding site cryo-EM glycan conformation glycan276 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0dffdf01c46c4651a77c53c885d4f689
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spelling	oai:doaj.org-article:0dffdf01c46c4651a77c53c885d4f6892021-11-04T04:29:10ZStructural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies2211-124710.1016/j.celrep.2021.109922https://doaj.org/article/0dffdf01c46c4651a77c53c885d4f6892021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013954https://doaj.org/toc/2211-1247Summary: 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.Christopher A. CottrellKartik ManneRui KongShuishu WangTongqing ZhouGwo-Yu ChuangRobert J. EdwardsRory HendersonKatarzyna JanowskaMegan KoppBob C. LinMark K. LouderAdam S. OliaReda RawiChen-Hsiang ShenJustin D. TaftJonathan L. TorresNelson R. WuBaoshan ZhangNicole A. Doria-RoseMyron S. CohenBarton F. HaynesLawrence ShapiroAndrew B. WardPriyamvada AcharyaJohn R. MascolaPeter D. KwongElsevierarticleantibody-antigen bindingantibody approach angleCD4 binding sitecryo-EMglycan conformationglycan276Biology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109922- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibody-antigen binding antibody approach angle CD4 binding site cryo-EM glycan conformation glycan276 Biology (General) QH301-705.5
spellingShingle	antibody-antigen binding antibody approach angle CD4 binding site cryo-EM glycan conformation glycan276 Biology (General) QH301-705.5 Christopher A. Cottrell Kartik Manne Rui Kong Shuishu Wang Tongqing Zhou Gwo-Yu Chuang Robert J. Edwards Rory Henderson Katarzyna Janowska Megan Kopp Bob C. Lin Mark K. Louder Adam S. Olia Reda Rawi Chen-Hsiang Shen Justin D. Taft Jonathan L. Torres Nelson R. Wu Baoshan Zhang Nicole A. Doria-Rose Myron S. Cohen Barton F. Haynes Lawrence Shapiro Andrew B. Ward Priyamvada Acharya John R. Mascola Peter D. Kwong Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
description	Summary: 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.
format	article
author	Christopher A. Cottrell Kartik Manne Rui Kong Shuishu Wang Tongqing Zhou Gwo-Yu Chuang Robert J. Edwards Rory Henderson Katarzyna Janowska Megan Kopp Bob C. Lin Mark K. Louder Adam S. Olia Reda Rawi Chen-Hsiang Shen Justin D. Taft Jonathan L. Torres Nelson R. Wu Baoshan Zhang Nicole A. Doria-Rose Myron S. Cohen Barton F. Haynes Lawrence Shapiro Andrew B. Ward Priyamvada Acharya John R. Mascola Peter D. Kwong
author_facet	Christopher A. Cottrell Kartik Manne Rui Kong Shuishu Wang Tongqing Zhou Gwo-Yu Chuang Robert J. Edwards Rory Henderson Katarzyna Janowska Megan Kopp Bob C. Lin Mark K. Louder Adam S. Olia Reda Rawi Chen-Hsiang Shen Justin D. Taft Jonathan L. Torres Nelson R. Wu Baoshan Zhang Nicole A. Doria-Rose Myron S. Cohen Barton F. Haynes Lawrence Shapiro Andrew B. Ward Priyamvada Acharya John R. Mascola Peter D. Kwong
author_sort	Christopher A. Cottrell
title	Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
title_short	Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
title_full	Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
title_fullStr	Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
title_full_unstemmed	Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
title_sort	structural basis of glycan276-dependent recognition by hiv-1 broadly neutralizing antibodies
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/0dffdf01c46c4651a77c53c885d4f689
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Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies

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