12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 7

Stephen C Harrison
Howard Hughes Med Inst and Children's Hosp, Harvard Med Sch, Boston, MA, USA

The HIV (and SIV) envelope glycoproteins, trimers of gp120/gp41, undergo a series of conformational transitions in response to ligands (receptor; co-receptor), thereby catalyzing membrane fusion and viral entry. Entry inhibitors retard or prevent these transitions. Structures of the monomeric core of gp120 in its CD4-bound conformation and of the trimeric ectodomain of gp41 in its postfusion conformation have been known for some time (1-3). A newly determined structure of an unliganded gp120 core (from SIVmac32H) shows that the “inner domain” of gp120 rearranges substantially during the transition to a CD4-bound conformation (4). The unliganded conformation includes a deep pocket, which on HIV gp120 probably accommodates entry inhibitors such as BMS-378806; the pocket disappears upon CD4 binding. The new structure also suggests possible gp120/gp41 interactions in the prefusion trimer and opens the way for design of locked-in gp120 variants, to help determine the antigenic properties of the molecule in a fixed state.

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