@article{Serrao:2014:nar/gku136,
author = {Serrao, E and Krishnan, L and Shun, M-C and Li, X and Cherepanov, P and Engelman, A and Maertens, GN},
doi = {nar/gku136},
journal = {Nucleic Acids Research},
pages = {5164--5176},
title = {Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding},
url = {http://dx.doi.org/10.1093/nar/gku136},
volume = {42},
year = {2014}
}

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TY  - JOUR
AB  - Retroviruses favor target-DNA (tDNA) distortion and particular bases at sites of integration, but the mechanism underlying HIV-1 selectivity is unknown. Crystal structures revealed a network of prototype foamy virus (PFV) integrase residues that distort tDNA: Ala188 and Arg329 interact with tDNA bases, while Arg362 contacts the phosphodiester backbone. HIV-1 integrase residues Ser119, Arg231, and Lys258 were identified here as analogs of PFV integrase residues Ala188, Arg329 and Arg362, respectively. Thirteen integrase mutations were analyzed for effects on integrase activity in vitro and during virus infection, yielding a total of 1610 unique HIV-1 integration sites. Purine (R)/pyrimidine (Y) dinucleotide sequence analysis revealed HIV-1 prefers the tDNA signature (0)RYXRY(4), which accordingly favors overlapping flexible dinucleotides at the center of the integration site. Consistent with roles for Arg231 and Lys258 in sequence specific and non-specific binding, respectively, the R231E mutation altered integration site nucleotide preferences while K258E had no effect. S119A and S119T integrase mutations significantly altered base preferences at positions −3 and 7 from the site of viral DNA joining. The S119A preference moreover mimicked wild-type PFV selectivity at these positions. We conclude that HIV-1 IN residue Ser119 and PFV IN residue Ala188 contact analogous tDNA bases to effect virus integration.
AU  - Serrao,E
AU  - Krishnan,L
AU  - Shun,M-C
AU  - Li,X
AU  - Cherepanov,P
AU  - Engelman,A
AU  - Maertens,GN
DO  - nar/gku136
EP  - 5176
PY  - 2014///
SN  - 0305-1048
SP  - 5164
TI  - Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gku136
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000336092300043&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://academic.oup.com/nar/article/42/8/5164/1071275
UR  - http://hdl.handle.net/10044/1/83890
VL  - 42
ER  - 

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