title: Structural insights into the retroviral DNA integration apparatus.
abstract: Retroviral replication depends on successful integration of the viral genetic material into a host cell chromosome. Virally encoded integrase, an enzyme from the DDE(D) nucleotidyltransferase superfamily, is responsible for the key DNA cutting and joining steps associated with this process. Insights into the structural and mechanistic aspects of integration are directly relevant for the development of antiretroviral drugs. Recent breakthroughs have led to biochemical and structural characterization of the principal integration intermediates revealing the tetramer of integrase that catalyzes insertion of both 3' viral DNA ends into a sharply bent target DNA. This review discusses the mechanism of retroviral DNA integration and the mode of action of HIV-1 integrase strand transfer inhibitors in light of the recent visualization of the prototype foamy virus intasome, target DNA capture and strand transfer complexes.
authors.affiliation: Division of Infectious Diseases, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, UK. p.cherepanov@imperial.ac.uk
authors.forename: Peter
authors.initials: P
authors.lastname: Cherepanov
authors.forename: Goedele N
authors.initials: GN
authors.lastname: Maertens
authors.forename: Stephen
authors.initials: S
authors.lastname: Hare
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D033481:Chromosomes, Mammalian / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D015497:HIV-1 / Q000737:chemistry / Q000201:enzymology; D019426:Integrases / Q000737:chemistry; D008958:Models, Molecular; D009698:Nucleoproteins / Q000737:chemistry; D011487:Protein Conformation; D011533:Proviruses / Q000235:genetics; D012190:Retroviridae / Q000235:genetics* / Q000378:metabolism*; D016092:Spumavirus / Q000737:chemistry / Q000201:enzymology; D016662:Virus Integration
chemical_list: D009698:Nucleoproteins; D019426:Integrases