Structure of an unliganded simian immunodeficiency virus gp120 core.
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 A 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.
Chen
Bing
B
Children's Hospital Laboratory of Molecular Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Vogan
Erik M
EM
Gong
Haiyun
H
Skehel
John J
JJ
Wiley
Don C
DC
Harrison
Stephen C
SC
D000595:Amino Acid Sequence; D001665:Binding Sites; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003460:Crystallization; D018360:Crystallography, X-Ray; D006031:Glycosylation; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000032:analysis; D011485:Protein Binding; D020836:Protein Structure, Quaternary / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000187:drug effects; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D014771:Virion / Q000737:chemistry / Q000378:metabolism
D015704:CD4 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus