Work

Hairpin Folding of HIV gp41 Abrogates Lipid Mixing Function at Physiologic pH and Inhibits Lipid Mixing by Exposed gp41 Constructs

Year: 2009

Type: article

Abstract: Conformational changes in the HIV gp41 protein are directly correlated with fusion between the HIV and target cell plasma membranes, which is the initial step of infection. Key gp41 fusion conformations include an early extended conformation termed prehairpin which contains exposed regions and a final low-energy conformation termed hairpin which has a compact six-helix bundle structure. Current fusion models debate the roles of hairpin and prehairpin conformations in the process of membrane merger. In the present work, gp41 constructs have been engineered which correspond to fusion relevant parts of both prehairpin and hairpin conformations and have been analyzed for their ability to induce lipid mixing between membrane vesicles. The data correlate membrane fusion function with the prehairpin conformation and suggest that one of the roles of the final hairpin conformation is sequestration of membrane-perturbing gp41 regions with consequent loss of the membrane disruption induced earlier by the prehairpin structure. To our knowledge, this is the first biophysical study to delineate the membrane fusion potential of gp41 constructs modeling key fusion conformations.

Source: Biochemistry

DOI: 10.1021/bi8019492

Authors: Kelly Sackett, Matthew J. Nethercott, Yechiel Shai, David P. Weliky

Institutions: Weizmann Institute of Science, Michigan State University

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Michigan State University, National Institute of Allergy and Infectious Diseases