Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Neutralizing epitopes in the membrane-proximal external region of hiv-1 gp41 are influenced by the transmembrane domain and the plasma membrane

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Montero, M.
  • Gulzar, N.
  • Klaric, K. A.
  • Donald, J. E.
  • Lepik, C.
  • Wu, S.
  • Tsai, S.
  • Julien, J. P.
  • Hessell, A. J.
  • Wang, S. X.
  • Lu, S.
  • Burton, Dennis
  • Pai, E. F.
  • DeGrado, W. F.
  • Scott, J. K.

publication date

  • March 2012

journal

  • Journal of Virology  Journal

abstract

  • Failure to elicit broadly neutralizing (bNt) antibodies (Abs) against the membrane-proximal external region of HIV-1 gp41 (MPER) reflects the difficulty of mimicking its neutralization-competent structure (NCS). Here, we analyzed MPER antigenicity in the context of the plasma membrane and identified a role for the gp41 transmembrane domain (TM) in exposing the epitopes of three bNt monoclonal Abs (MAbs) (2F5, 4E10, and Z13e1). We transiently expressed DNA constructs encoding gp41 ectodomain fragments fused to either the TM of the platelet-derived growth factor receptor (PDGFR) or the gp41 TM and cytoplasmic tail domain (CT). Constructs encoding the MPER tethered to the gp41 TM followed by a 27-residue CT fragment (MPER-TM1) produced optimal MAb binding. Critical binding residues for the three Nt MAbs were identified using a panel of 24 MPER-TM1 mutants bearing single amino acid substitutions in the MPER; many were previously shown to affect MAb-mediated viral neutralization. Moreover, non-Nt mutants of MAbs 2F5 and 4E10 exhibited a reduction in binding to MPER-TM1 and yet maintained binding to synthetic MPER peptides, indicating that MPER-TM1 better approximates the MPER NCS than peptides. Replacement of the gp41 TM and CT of MPER-TM1 with the PDGFR TM reduced binding by MAb 4E10, but not 2F5, indicating that the gp41 TM plays a pivotal role in orienting the 4E10 epitope, and more globally, in affecting MPER exposure.

subject areas

  • Animals
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Cell Line
  • Cell Membrane
  • Epitopes
  • HIV Envelope Protein gp41
  • HIV Infections
  • HIV-1
  • Humans
  • Protein Structure, Tertiary
scroll to property group menus

Identity

PubMed Central ID

  • PMC3302331

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.06349-11

PubMed ID

  • 22238313
scroll to property group menus

Additional Document Info

start page

  • 2930

end page

  • 2941

volume

  • 86

issue

  • 6

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support