Download MendeleyStructure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody.
Kwong, P.D., Wyatt, R., Robinson, J., Sweet, R.W., Sodroski, J., Hendrickson, W.A.(1998) Nature 393: 648-659
- PubMed: 9641677
- DOI: https://doi.org/10.1038/31405
- Primary Citation of Related Structures:
1GC1 - PubMed Abstract:
The entry of human immunodeficiency virus (HIV) into cells requires the sequential interaction of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. These interactions initiate a fusion of the viral and cellular membranes. Although gp120 can elicit virus-neutralizing antibodies, HIV eludes the immune system. We have solved the X-ray crystal structure at 2.5 A resolution of an HIV-1 gp120 core complexed with a two-domain fragment of human CD4 and an antigen-binding fragment of a neutralizing antibody that blocks chemokine-receptor binding. The structure reveals a cavity-laden CD4-gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion. Our results provide a framework for understanding the complex biology of HIV entry into cells and should guide efforts to intervene.
Organizational Affiliation:
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
