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Crystal structure of an HIV-binding recombinant fragment of human CD4
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032.
Insights
The structure of CD4, a T cell protein crucial for immune response and HIV entry, reveals two associated immunoglobulin-like domains. Key HIV binding sites are located in domain D1, with domain D2 showing unique structural features.
Area of Science:
- Structural Biology
- Immunology
- Virology
Background:
- CD4 glycoprotein is vital for T cell-mediated immune responses.
- CD4 serves as the primary receptor for Human Immunodeficiency Virus (HIV) entry into host cells.
Purpose of the Study:
- To determine the high-resolution structure of a soluble CD4 fragment.
- To elucidate the structural basis of CD4's interaction with HIV.
Main Methods:
- X-ray crystallography at 2.3 A resolution.
Main Results:
- The soluble CD4 fragment comprises two closely associated immunoglobulin-like domains.
- Domain D1 contains residues critical for HIV recognition, identified through mutant analysis and antibody binding studies.
- Domain D2 exhibits distinct structural characteristics, including variations in beta-strand topology and an intra-sheet disulfide bridge.
Conclusions:
- The determined structure provides a detailed molecular understanding of CD4.
- This structural insight is crucial for understanding HIV's mechanism of infection and for developing therapeutic strategies.
Abstract:
CD4 glycoprotein on the surface of T cells helps in the immune response and is the receptor for HIV infection. The structure of a soluble fragment of CD4 determined at 2.3 A resolution reveals that the molecule has two intimately associated immunoglobulin-like domains. Residues implicated in HIV recognition by analysis of mutants and antibody binding are salient features in domain D1. Domain D2 is distinguished by a variation on the beta-strand topologies of antibody domains and by an intra-sheet disulphide bridge.