title: HIV integrase structure and function.
abstract: HIV integrase consists of three domains, the structures of which have been individually determined by X-ray crystallography or NMR spectroscopy. The core domain, spanning residues 50-212, is responsible for the catalytic activity of the enzyme. The crystal structure of a dimer of this domain shows similarity to other proteins that carry out polynucleotidyl transfer, including MuA transposase and RNase H. The small N-terminal domain folds into a dimeric helix-turn-helix structure, which is stabilized by the coordination of zinc with conserved His and Cys residues. The function of this domain is unclear; however, it is required for integration activity and enhances tetramerization in the context of the full-length integrase. The C-terminal domain, which has an SH3-like fold, is involved in DNA binding. The structure of this domain reveals a large saddle-shaped cleft that is formed by dimerization. This cleft contains a number of positively charged residues, and its dimensions are appropriate for accommodating a double-stranded DNA helix. Although the C-terminal domain was originally believed to be involved in target DNA binding, more recent evidence suggests that it may bind to both the ends of the viral DNA and to the target DNA. Although the individual domain structures provide some insights into the function of the protein, a more detailed understanding of the complete mechanism by which integrase binds, cleaves, and transfers DNA requires a greater knowledge of how these domains are arranged in the active multimer.
authors.affiliation: Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: D
authors.initials: D
authors.lastname: Esposito
authors.forename: R
authors.initials: R
authors.lastname: Craigie
mesh_terms: D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D004247:DNA / Q000378:metabolism; D019427:HIV Integrase / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D015032:Zinc
chemical_list: D004247:DNA; D019427:HIV Integrase; D015032:Zinc