The variable N-terminal region of DDX5 contains structural elements and auto-inhibits its interaction with NS5B of hepatitis C virus

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dc.contributor.authorDutta, Sujit
dc.contributor.authorGupta, Garvita
dc.contributor.authorChoi, Yook-Wah
dc.contributor.authorKotaka, Masayo
dc.contributor.authorFielding, Burtram C.
dc.contributor.authorSong, Jianxing
dc.contributor.authorTan, Yee-Joo
dc.date.accessioned2013-11-26T12:50:24Z
dc.date.available2013-11-26T12:50:24Z
dc.date.issued2012
dc.description.abstractRNA helicases of the DEAD (Asp-Glu-Ala-Asp)-box family of proteins are involved in many aspects of RNA metabolism from transcription to RNA decay, but most of them have also been shown to be multifunctional. The DEAD-box helicase DDX5 of host cells has been shown to interact with the RNA-dependent RNA polymerase (NS5B) of HCV (hepatitis C virus). In the present study, we report the presence of two independent NS5Bbinding sites in DDX5, one located at the N-terminus and another at the C-terminus. The N-terminal fragment of DDX5, which consists of the first 305 amino acids and shall be referred as DDX5-N, was expressed and crystallized. The crystal structure shows that domain 1 (residues 79–303) of DDX5 contains the typical features found in the structures of other DEADbox helicases. DDX5-N also contains the highly variable NTR (N-terminal region) of unknown function and the crystal structure reveals structural elements in part of the NTR, namely residues 52–78. This region forms an extensive loop and an α-helix. From co-immunoprecipitation experiments, the NTR of DDX5-N was observed to auto-inhibit its interaction with NS5B. Interestingly, the α-helix in NTR is essential for this auto-inhibition and seems to mediate the interaction between the highly flexible 1–51 residues in NTR and the NS5B-binding site in DDX5-N. Furthermore, NMR investigations reveal that there is a direct interaction between DDX5 and NS5B in vitro.en_US
dc.description.accreditationWeb of Scienceen_US
dc.identifier.citationDutta, S. (2012). The variable N-terminal region of DDX5 contains structural elements and auto-inhibits its interaction with NS5B of hepatitis C virus. Biochemical Journal, 446: 37–46en_US
dc.identifier.issn0264-6021
dc.identifier.urihttp://hdl.handle.net/10566/864
dc.language.isoenen_US
dc.privacy.showsubmitterfalse
dc.publisherPortland Pressen_US
dc.rights© 2012 Portland Press
dc.source.urihttp://dx.doi.org/10.1042/BJ20120001
dc.status.ispeerreviewedtrue
dc.subjectAuto-inhibitionen_US
dc.subjectDDX5en_US
dc.subjectDEAD-box familyen_US
dc.subjectHepatitis C virusen_US
dc.subjectNS5Ben_US
dc.subjectN-terminal regionen_US
dc.titleThe variable N-terminal region of DDX5 contains structural elements and auto-inhibits its interaction with NS5B of hepatitis C virusen_US
dc.typeArticleen_US

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