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

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 28

Bing Chen², E Vogan^1,2, H Gong², J Skehel³, D Wiley^1,2, and S Harrison^1,2
1Howard Hughes Med Inst, Boston, MA, USA; ²Children's Hosp, Harvard Med Sch, Boston, MA, USA ; and ³Natl Inst of Med Res, London, UK

BACKGROUND: Envelope glycoproteins of HIV and simian immunodeficiency virus (SIV) catalyze fusion of viral and cellular membranes by undergoing a series of conformational changes that are induced by binding receptor (CD4) and co-receptor (e.g., CCR5 or CXCR4) on the surface of host cells.

METHODS: We have recently determined the crystal structure, at 3.9-Å resolution, of a fully glycosylated and unliganded SIV gp120 core, in a conformation representing its pre-fusion state.

RESULTS: Comparison of the new structure and the HIV gp120 core in the CD4-bound conformation reveals a striking structural rearrangement in parts of the protein. The 2 conformations of gp120 present distinct antigenic surfaces. We have also identified the binding site for a compound (BMS-378806) that inhibits viral entry, and proposed a model for events that accompany receptor engagement of an envelope glycoprotein trimer. We have now produced stabilized forms of unliganded SIV gp120 by introduction of additional disulfide bonds.

CONCLUSIONS: These disulfide-locked mutants are expected to facilitate further crystallographic studies on both the monomeric gp120 and the envelope glycoprotein trimers. They may also be used as selective immunnogens.

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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.