Structure of the Membrane Proximal External Region of HIV-1 Envelope Glycoprotein

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2018 Sep 7

PMID 30185554

Citations 43

Authors

Qingshan Fu

Md Munan Shaik

Yongfei Cai

Fadi Ghantous

Alessandro Piai

Hanqin Peng

Sophia Rits-Volloch

Zhijun Liu

Stephen C Harrison

Michael S Seaman

Bing Chen

James J Chou

Affiliations

Soon will be listed here.

Abstract

The membrane-proximal external region (MPER) of the HIV-1 envelope glycoprotein (Env) bears epitopes of broadly neutralizing antibodies (bnAbs) from infected individuals; it is thus a potential vaccine target. We report an NMR structure of the MPER and its adjacent transmembrane domain in bicelles that mimic a lipid-bilayer membrane. The MPER lies largely outside the lipid bilayer. It folds into a threefold cluster, stabilized mainly by conserved hydrophobic residues and potentially by interaction with phospholipid headgroups. Antigenic analysis and comparison with published images from electron cryotomography of HIV-1 Env on the virion surface suggest that the structure may represent a prefusion conformation of the MPER, distinct from the fusion-intermediate state targeted by several well-studied bnAbs. Very slow bnAb binding indicates that infrequent fluctuations of the MPER structure give these antibodies occasional access to alternative conformations of MPER epitopes. Mutations in the MPER not only impede membrane fusion but also influence presentation of bnAb epitopes in other regions. These results suggest strategies for developing MPER-based vaccine candidates.

Citing Articles

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