Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 Apr 27

PMID 27114034

Citations 284

Authors

Guillaume B E Stewart-Jones

Cinque Soto

Thomas Lemmin

Gwo-Yu Chuang

Aliaksandr Druz

Rui Kong

Paul V Thomas

Kshitij Wagh

Tongqing Zhou

Anna-Janina Behrens

Tatsiana Bylund

Chang W Choi

Jack R Davison

Ivelin S Georgiev

M Gordon Joyce

Young Do Kwon

Marie Pancera

Justin Taft

Yongping Yang

Baoshan Zhang

Sachin S Shivatare

Vidya S Shivatare

Chang-Chun D Lee

Chung-Yi Wu

Carole A Bewley

Dennis R Burton

Wayne C Koff

Mark Connors

Max Crispin

Ulrich Baxa

Bette T Korber

Chi-Huey Wong

John R Mascola

Peter D Kwong

Affiliations

Soon will be listed here.

Abstract

The HIV-1-envelope (Env) trimer is covered by a glycan shield of ∼90 N-linked oligosaccharides, which comprises roughly half its mass and is a key component of HIV evasion from humoral immunity. To understand how antibodies can overcome the barriers imposed by the glycan shield, we crystallized fully glycosylated Env trimers from clades A, B, and G, visualizing the shield at 3.4-3.7 Å resolution. These structures reveal the HIV-1-glycan shield to comprise a network of interlocking oligosaccharides, substantially ordered by glycan crowding, that encase the protein component of Env and enable HIV-1 to avoid most antibody-mediated neutralization. The revealed features delineate a taxonomy of N-linked glycan-glycan interactions. Crowded and dispersed glycans are differently ordered, conserved, processed, and recognized by antibody. The structures, along with glycan-array binding and molecular dynamics, reveal a diversity in oligosaccharide affinity and a requirement for accommodating glycans among known broadly neutralizing antibodies that target the glycan-shielded trimer.

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