Structure-function studies of the self-assembly domain of the human immunodeficiency virus type 1 transmembrane protein gp41

The coiled-coil region of the human immunodeficiency virus type 1 transmemb rane protein (gp41) makes up the interior core of the six-helix bundle stru cture of the gp41 self-assembly domain. We extended our previous study of t his domain (Y. Weng and C. D. Weiss, J. Virol. 72:9676-9682, 1998) by analy zing 23 additional mutants at positions that lie at the interface of the in terior core and outer helices. We found nine new functional mutants. For mo st mutants, the activity could be explained by the ability of the modeled m utants to stabilize the six-helix bundle structure. The present study provi des insights into the envelope glycoprotein fusion mechanism and informatio n for rational drug and vaccine design.