| Literature DB >> 27114034 |
Guillaume B E Stewart-Jones1, Cinque Soto1, Thomas Lemmin2, Gwo-Yu Chuang1, Aliaksandr Druz1, Rui Kong1, Paul V Thomas1, Kshitij Wagh3, Tongqing Zhou1, Anna-Janina Behrens4, Tatsiana Bylund1, Chang W Choi1, Jack R Davison5, Ivelin S Georgiev1, M Gordon Joyce1, Young Do Kwon1, Marie Pancera1, Justin Taft1, Yongping Yang1, Baoshan Zhang1, Sachin S Shivatare6, Vidya S Shivatare6, Chang-Chun D Lee6, Chung-Yi Wu6, Carole A Bewley5, Dennis R Burton7, Wayne C Koff8, Mark Connors9, Max Crispin4, Ulrich Baxa10, Bette T Korber3, Chi-Huey Wong11, John R Mascola1, Peter D Kwong12.
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.Entities:
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Year: 2016 PMID： 27114034 PMCID： PMC5543418 DOI： 10.1016/j.cell.2016.04.010
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582