Monoclonal antibodies that bind to the core of fusion-active glycoprotein 41.

Published

Journal Article

The heptad repeat regions HR1 and HR2 of HIV-1 gp41 can associate to form heterooligomers through helical coil-coil interactions that are believed to play a key role in virus-induced membrane fusion. The HR1/HR2 complex was proposed to be the core structure of the fusion-active conformation of gp41. Here, we show that two human monoclonal antibodies, Fab-d and 50-69, specifically recognize the putative fusion-active conformation of gp41. Fab-d binding requires the interaction between the HR1 and HR2 regions of gp41. The reactivity of human monoclonal antibody 50-69 to the C terminus of the HR1 sequence is dependent on the helical structure of HR1. It appears that HR2 is able to interact with HR1 and, subsequently, induce an epitope in HR1 that is required for 50-69 binding. Mutations that disrupt the helical structure of HR1 significantly compromise Fab-d and 50-69 binding. Although the epitopes are not identical, the ability of Fab-d to partially compete with 50-69 binding suggests a close proximity of the two epitopes. Antibodies that are able to interact with the core of the putative fusion-active gp41 may be useful in further unveiling the mechanism of HIV-induced membrane fusion.

Full Text

Duke Authors

Cited Authors

  • Chen, CH; Greenberg, ML; Bolognesi, DP; Matthews, TJ

Published Date

  • December 10, 2000

Published In

Volume / Issue

  • 16 / 18

Start / End Page

  • 2037 - 2041

PubMed ID

  • 11153086

Pubmed Central ID

  • 11153086

International Standard Serial Number (ISSN)

  • 0889-2229

Digital Object Identifier (DOI)

  • 10.1089/088922200750054765

Language

  • eng

Conference Location

  • United States