Division of Labor Within Human Immunodeficiency Virus Integrase Complexes: Determinants of Catalysis and Target DNA Capture

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2005 Nov 25

PMID 16306609

Citations 7

Authors

Tracy L Diamond

Frederic D Bushman

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Influence of the amino-terminal sequence on the structure and function of HIV integrase.

Eilers G, Gupta K, Allen A, Zhou J, Hwang Y, Cory M Retrovirology. 2020; 17(1):28.

PMID: 32867805 PMC: 7457537. DOI: 10.1186/s12977-020-00537-x.

Insight into the ERVK Integrase - Propensity for DNA Damage.

Bray S, Turnbull M, Hebert S, Douville R Front Microbiol. 2016; 7:1941.

PMID: 27990140 PMC: 5131560. DOI: 10.3389/fmicb.2016.01941.

Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function.

Ballandras-Colas A, Brown M, Cook N, Dewdney T, Demeler B, Cherepanov P Nature. 2016; 530(7590):358-61.

PMID: 26887496 PMC: 4908968. DOI: 10.1038/nature16955.

Structural properties of HIV integrase. Lens epithelium-derived growth factor oligomers.

Gupta K, Diamond T, Hwang Y, Bushman F, Van Duyne G J Biol Chem. 2010; 285(26):20303-15.

PMID: 20406807 PMC: 2888443. DOI: 10.1074/jbc.M110.114413.

In vitro initial attachment of HIV-1 integrase to viral ends: control of the DNA specific interaction by the oligomerization state.

Lesbats P, Metifiot M, Calmels C, Baranova S, Nevinsky G, Andreola M Nucleic Acids Res. 2008; 36(22):7043-58.

PMID: 18987001 PMC: 2602759. DOI: 10.1093/nar/gkn796.

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