Journal Article

Structural basis for membrane anchoring of HIV-1 envelope spike

Chen, Bing, Park, Donghyun, Chang, Weiting, Frey, Gary, Herrmann, Tobias, Chou, James J., Dev, Jyoti, Chen, Jia, Ha, Heather Jiwon, Ghantous, Fadi, Seaman, Michael S., Liu, Zhijun, Fu, Qingshan

2016

Overview

HIV-1 envelope spike (Env) is a type I membrane protein that mediates viral entry. We used nuclear magnetic resonance to determine an atomic structure of the transmembrane (TM) domain of HIV-1 Env reconstituted in bicelles that mimic a lipid bilayer. The TM forms a well-ordered trimer that protects a conserved membrane-embedded arginine. An amino-terminal coiled-coil and a carboxyl-terminal hydrophilic core stabilize the trimer. Individual mutations of conserved residues did not disrupt the TM trimer and minimally affected membrane fusion and infectivity. Major changes in the hydrophilic core, however, altered the antibody sensitivity of Env. These results show how a TM domain anchors, stabilizes, and modulates a viral envelope spike and suggest that its influence on Env conformation is an important consideration for HIV-1 immunogen design.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Antibodies / Arginine - chemistry / Arginine - genetics / Design / Envelopes / HIV / HIV Antibodies - immunology / HIV Envelope Protein gp41 - chemistry / HIV Envelope Protein gp41 - genetics / HIV Envelope Protein gp41 - immunology / HIV-1 - immunology / HIV-1 - physiology / Human immunodeficiency virus / Lentivirus / Lipid Bilayers - chemistry / Lipids / Membrane Fusion / Membranes / Mutation / NMR / Nuclear magnetic resonance / Nuclear Magnetic Resonance, Biomolecular / Protein Multimerization / Protein Stability / Protein Structure, Tertiary / Proteins / Spikes / Trimers / Vaccines / Virus Internalization