Editing Integrase (section)

== Structure ==
All retroviral IN proteins contain three canonical domains, connected by flexible linkers:<ref name=":0">{{cite journal | vauthors = Jóźwik IK, Passos DO, Lyumkis D | title = Structural Biology of HIV Integrase Strand Transfer Inhibitors | journal = Trends in Pharmacological Sciences | volume = 41 | issue = 9 | pages = 611–626 | date = September 2020 | pmid = 32624197 | doi = 10.1016/j.tips.2020.06.003 | pmc = 7429322 }}</ref><ref name=":1">{{cite journal | vauthors = Delelis O, Carayon K, Saïb A, Deprez E, Mouscadet JF | title = Integrase and integration: biochemical activities of HIV-1 integrase | journal = Retrovirology | volume = 5 | issue = 1 | pages = 114 | date = December 2008 | pmid = 19091057 | pmc = 2615046 | doi = 10.1186/1742-4690-5-114 | doi-access = free }}</ref>

* an [[N-terminal]] HH-CC zinc-binding domain (a three-helical bundle stabilized by coordination of a Zn(II) cation),
* a catalytic core domain (RNaseH fold),
* a [[C-terminal]] DNA-binding domain ([[SH3 domain|SH3 fold]]).

Crystal and NMR structures of the individual domains and 2-domain constructs of integrases from HIV-1, HIV-2, [[Simian immunodeficiency virus|SIV]], and [[Rous Sarcoma Virus]] (RSV) have been reported, with the first structures determined in 1994.<ref>{{cite journal | vauthors = Lodi PJ, Ernst JA, Kuszewski J, Hickman AB, Engelman A, Craigie R, Clore GM, Gronenborn AM | display-authors = 6 | title = Solution structure of the DNA binding domain of HIV-1 integrase | journal = Biochemistry | volume = 34 | issue = 31 | pages = 9826–9833 | date = August 1995 | pmid = 7632683 | doi = 10.1021/bi00031a002 }}</ref><ref name=":2">{{cite journal | vauthors = Choi E, Mallareddy JR, Lu D, Kolluru S | title = Recent advances in the discovery of small-molecule inhibitors of HIV-1 integrase | journal = Future Science OA | volume = 4 | issue = 9 | pages = FSO338 | date = October 2018 | pmid = 30416746 | doi = 10.4155/fsoa-2018-0060 | pmc = 6222271 }}</ref> Biochemical data and structural data suggest that retroviral IN functions as a [[Tetrameric protein|tetramer]] (dimer-of-dimers), with all three domains being important for multimerization and viral DNA binding.<ref>{{cite journal | vauthors = Hare S, Di Nunzio F, Labeja A, Wang J, Engelman A, Cherepanov P | title = Structural basis for functional tetramerization of lentiviral integrase | journal = PLOS Pathogens | volume = 5 | issue = 7 | pages = e1000515 | date = July 2009 | pmid = 19609359 | doi = 10.1371/journal.ppat.1000515 | pmc = 2705190 | editor-first = Jeremy | editor-last = Luban | doi-access = free }}</ref> In addition, several host cellular proteins have been shown to interact with IN to facilitate the integration process: e.g., the host factor, human chromatin-associated protein [[PSIP1|LEDGF]], tightly binds HIV IN and directs the HIV pre-integration complex towards highly expressed genes for integration.<ref>{{cite journal | vauthors = Craigie R, Bushman FD | title = HIV DNA integration | journal = Cold Spring Harbor Perspectives in Medicine | volume = 2 | issue = 7 | pages = a006890 | date = July 2012 | pmid = 22762018 | pmc = 3385939 | doi = 10.1101/cshperspect.a006890 }}</ref>

[[Human foamy virus]] (HFV), an agent harmless to humans, has an integrase similar to HIV IN and is therefore a model of HIV IN function; a 2010 crystal structure of the HFV integrase assembled on viral DNA ends has been determined.<ref name=":2" />