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

TitleThe variable N-terminal region of DDX5 contains structural elements and auto-inhibits its interaction with NS5B of hepatitis C virus
Authors
KeywordsDDX5 enzyme
DEAD box protein
Alpha helix
Amino terminal sequence
Chromatin immunoprecipitation
Issue Date2012
PublisherPortland Press Ltd.. The Journal's web site is located at http://www.biochemj.org/bj/default.htm
Citation
Biochemical Journal, 2012, v. 446 n. 1, p. 37-46 How to Cite?
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 NS5B-binding 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 DEAD-box 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 alpha-helix. From co-immunoprecipitation experiments, the NTR of DDX5-N was observed to auto-inhibit its interaction with NS5B. Interestingly, the alpha-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.
Persistent Identifierhttp://hdl.handle.net/10722/149134
ISSN
2015 Impact Factor: 3.562
2015 SCImago Journal Rankings: 2.582
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDutta, Sen_US
dc.contributor.authorGupta, Gen_US
dc.contributor.authorChoi, YWen_US
dc.contributor.authorKotaka, Men_US
dc.contributor.authorFielding, BCen_US
dc.contributor.authorSong, Jen_US
dc.contributor.authorTan, YJen_US
dc.date.accessioned2012-06-22T06:25:09Z-
dc.date.available2012-06-22T06:25:09Z-
dc.date.issued2012en_US
dc.identifier.citationBiochemical Journal, 2012, v. 446 n. 1, p. 37-46en_US
dc.identifier.issn0264-6021-
dc.identifier.urihttp://hdl.handle.net/10722/149134-
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 NS5B-binding 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 DEAD-box 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 alpha-helix. From co-immunoprecipitation experiments, the NTR of DDX5-N was observed to auto-inhibit its interaction with NS5B. Interestingly, the alpha-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.-
dc.languageengen_US
dc.publisherPortland Press Ltd.. The Journal's web site is located at http://www.biochemj.org/bj/default.htm-
dc.relation.ispartofBiochemical Journalen_US
dc.rightsThe final version of record is available at [http://www.biochemj.org/bj/default.htm].-
dc.subjectDDX5 enzyme-
dc.subjectDEAD box protein-
dc.subjectAlpha helix-
dc.subjectAmino terminal sequence-
dc.subjectChromatin immunoprecipitation-
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
dc.identifier.emailKotaka, M: masayo@hku.hken_US
dc.identifier.emailTan, YJ: Yee_Joo_TAN@NUHS.edu.sg-
dc.identifier.authorityKotaka, M=rp00293en_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1042/BJ20120001-
dc.identifier.pmid22640416-
dc.identifier.scopuseid_2-s2.0-84864755881-
dc.identifier.hkuros200285en_US
dc.identifier.volume446-
dc.identifier.issue1-
dc.identifier.spage37-
dc.identifier.epage46-
dc.identifier.eissn1470-8728-
dc.identifier.isiWOS:000307626300004-
dc.publisher.placeUnited Kingdom-

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