Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Academic Article uri icon

Overview

abstract

  • The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 Å resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation.

publication date

  • October 8, 2014

Research

keywords

  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41

Identity

PubMed Central ID

  • PMC4348022

Scopus Document Identifier

  • 84909640954

Digital Object Identifier (DOI)

  • 10.1038/nature13808

PubMed ID

  • 25296255

Additional Document Info

volume

  • 514

issue

  • 7523