1. Children's Hospital Laboratory of Molecular Medicine, Harvard Medical School, and
2. Howard Hughes Medical Institute, 320 Longwood Avenue, Boston, Massachusetts 02115, USA
3. National Institute of Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
4. Deceased

Correspondence to: Stephen C. Harrison^1,2 Correspondence and requests for materials should be addressed to S.C.H. (Email: harrison@crystal.harvard.edu).
Coordinates and structure factors have been deposited in the PDB, accession number 2BF1.

Abstract

Envelope glycoproteins of human and simian immunodeficiency virus (HIV and SIV) undergo a series of conformational changes when they interact with receptor (CD4) and co-receptor on the surface of a potential host cell, leading ultimately to fusion of viral and cellular membranes. Structures of fragments of gp120 and gp41 from the envelope protein are known, in conformations corresponding to their post-attachment and postfusion states, respectively. We report the crystal structure, at 4 Å resolution, of a fully glycosylated SIV gp120 core, in a conformation representing its prefusion state, before interaction with CD4. Parts of the protein have a markedly different organization than they do in the CD4-bound state. Comparison of the unliganded and CD4-bound structures leads to a model for events that accompany receptor engagement of an envelope glycoprotein trimer. The two conformations of gp120 also present distinct antigenic surfaces. We identify the binding site for a compound that inhibits viral entry.

1. Children's Hospital Laboratory of Molecular Medicine, Harvard Medical School, and
2. Howard Hughes Medical Institute, 320 Longwood Avenue, Boston, Massachusetts 02115, USA
3. National Institute of Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
4. Deceased

Correspondence to: Stephen C. Harrison^1,2 Correspondence and requests for materials should be addressed to S.C.H. (Email: harrison@crystal.harvard.edu).
Coordinates and structure factors have been deposited in the PDB, accession number 2BF1.

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