Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
The beta 20-beta 21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions
Nature communications, v 8
19 Oct 2017
PMID: 29051495
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally "closed" State 1 to more "open" conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements. We identify the gp120 beta 20-beta 21 element as a major regulator of Env transitions. Several amino acid changes in the beta 20-beta 21 base lead to open Env conformations, recapitulating the structural changes induced by CD4 binding. These HIV-1 mutants require less CD4 to infect cells and are relatively resistant to State 1-preferring broadly neutralizing antibodies. These data provide insights into the molecular mechanism and vulnerability of HIV-1 entry.
Metrics
Details
- Title
- The beta 20-beta 21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions
- Creators
- Alon Herschhorn - Harvard UniversityChristopher Gu - Dana-Farber Cancer InstituteFrancesca Moraca - Drexel UniversityXiaochu Ma - Yale UniversityMark Farrell - University of PennsylvaniaAmos B. Smith - University of PennsylvaniaMarie Pancera - Vaccine Research CenterPeter D. Kwong - Vaccine Research CenterArne Schon - Johns Hopkins UniversityErnesto Freire - Johns Hopkins UniversityCameron Abrams - Drexel UniversityScott C. Blanchard - Cornell UniversityWalther Mothes - Yale UniversityJoseph G. Sodroski - Harvard University
- Publication Details
- Nature communications, v 8
- Publisher
- Springer Nature
- Number of pages
- 12
- Grant note
- UM1AI100645 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) 109285-58-RKVA / Phase II amfAR research grant 108501-53-RKNT / amfAR Mathilde Krim Fellowship in Basic Biomedical Research AI24755; AI124982; P01 GM56550; AI100645; GM116654; GM098859 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM098859 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000413197100009
- Scopus ID
- 2-s2.0-85031943201
- Other Identifier
- 991019168305204721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Multidisciplinary Sciences