dc.contributor.author | Dutta, Sujit | |
dc.contributor.author | Gupta, Garvita | |
dc.contributor.author | Choi, Yook-Wah | |
dc.contributor.author | Kotaka, Masayo | |
dc.contributor.author | Fielding, Burtram C. | |
dc.contributor.author | Song, Jianxing | |
dc.contributor.author | Tan, Yee-Joo | |
dc.date.accessioned | 2013-11-26T12:50:24Z | |
dc.date.available | 2013-11-26T12:50:24Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Dutta, 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: 37–46 | en_US |
dc.identifier.issn | 0264-6021 | |
dc.identifier.uri | http://hdl.handle.net/10566/864 | |
dc.description.abstract | RNA 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.language.iso | en | en_US |
dc.publisher | Portland Press | en_US |
dc.rights | © 2012 Portland Press | |
dc.source.uri | http://dx.doi.org/10.1042/BJ20120001 | |
dc.subject | Auto-inhibition | en_US |
dc.subject | DDX5 | en_US |
dc.subject | DEAD-box family | en_US |
dc.subject | Hepatitis C virus | en_US |
dc.subject | NS5B | en_US |
dc.subject | N-terminal region | en_US |
dc.title | The variable N-terminal region of DDX5 contains structural elements and auto-inhibits its interaction with NS5B of hepatitis C virus | en_US |
dc.type | Article | en_US |
dc.privacy.showsubmitter | false | |
dc.status.ispeerreviewed | true | |
dc.description.accreditation | Web of Science | en_US |