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.

Keywords: gp120; SIV; structure