Photo-cross-linking studies suggest a model for the architecture of an active human immunodeficiency virus type 1 integrase-DNA complex. NLM AIDSLINE Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

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Photo-cross-linking studies suggest a model for the architecture of an active human immunodeficiency virus type 1 integrase-DNA complex.

Biochemistry. 1998 May 12;37(19):6667-78. Unique Identifier : AIDSLINE MED/98244844
Heuer TS; Brown PO; Department of Biochemistry, Program in Cancer Biology, Stanford; University Medical Center, California 94305-5428, USA.


Abstract: The virally encoded integrase protein carries out retroviral integration, which requires specific interactions with the two ends of the viral DNA, and also with host DNA that is the target of integration. We attached a photo-cross-linking agent to specific viral and target DNA sites to identify regions of the integrase polypeptide that are in close proximity to those substrate features in the active integrase-DNA complex. The active form of integrase is a multimer. The higher-order organization of the active integration complex was therefore investigated by determining whether specific cross-links occurred to the active-site containing protomer. Both viral and target DNA cross-links to human immunodeficiency virus type 1 (HIV-1) integrase mapped predominantly to integrase protomers in trans to the active site, in a multimeric integrase complex. The results provide the basis for a model of the protein-DNA architecture of an active HIV-1 integration complex that suggests specific functions for the N-terminal, core, and C-terminal domains of retroviral integrase. One implication of this model is that the integrase multimer that mediates concerted integration of the viral DNA ends is composed of at least eight integrase protomers.
Keywords: *Cross-Linking Reagents/CHEMISTRY *DNA, Viral/CHEMISTRY *HIV Integrase/CHEMISTRY *HIV-1/ENZYMOLOGY *Models, MolecularKWDcross-linkingreagents/chemistryKWDdna,viral/chemistryKWDhivintegrase/chemistryKWDhiv-1/enzymologyKWDmodels,molecular
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Copyright © 1998 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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