Capture of an early fusion-active conformation of HIV-1 gp41
Rika A. Furuta1, Carl T. Wild2, Yongkai Weng1
& Carol D. Weiss1, 3
1Office of Vaccines, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Bldg. 29, Room 532, HFM-413, 29 Lincoln Dr., Bethesda, Maryland 20892-4555, USA.
2Biotech Research Laboratories, 217 Perry Parkway, Gaithersburg, Maryland 20877, USA.
3email: cdweiss@helix.nih.gov
Using an inhibitory synthetic peptide (DP-178) from HIV-1 gp41, we have trapped HIV-1 envelope glycoprotein (Env) undergoing conformational changes during virus entry. Our data show that DP-178 binds gp41 and inhibits Env-mediated membrane fusion after gp120 interacts with cellular receptors, indicating that conformational changes involving the coiled coil domain of gp41 are required for entry. Capture of this fusion-active conformation of Env provides insights into the early events leading to Env-mediated membrane fusion.