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Journal of Virology, December 2005, p. 15376-15387, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15376-15387.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Division of Labor within Human Immunodeficiency Virus Integrase Complexes: Determinants of Catalysis and Target DNA Capture{dagger}

Tracy L. Diamond and Frederic D. Bushman*

University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104-6076

Received 20 July 2005/ Accepted 27 September 2005

Following the completion of reverse transcription, the human immunodeficiency virus integrase (IN) enzyme covalently links the viral cDNA to a host cell chromosome. An IN multimer carries out this reaction, but the roles of individual monomers within the complex are mostly unknown. Here we analyzed the distribution of functions for target DNA capture and catalysis within the IN multimer. We used forced complementation between pairs of IN deletion derivatives in vitro as a tool for probing cis-trans relationships and analyzed amino acid substitutions affecting either catalysis or target site selection within these complementing complexes. This allowed the demonstration that the IN variant contributing the active catalytic domain was also responsible for recognition of the integration target DNA. We were further able to establish that a single monomer is responsible for both functions by use of assay mixtures containing three different IN genotypes. These data specify the ligands bound at the catalytically relevant IN monomer and allow more-specific modeling of the mechanism of inhibitors that also bind this surface of IN.

* Corresponding author. Mailing address: University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104-6076. Phone: (215) 573-8732. Fax: (215) 573-4856. E-mail: bushman{at}mail.med.upenn.edu.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org.

Journal of Virology, December 2005, p. 15376-15387, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15376-15387.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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Copyright © 2005 by the American Society for Microbiology. All rights reserved.