4A4D

Crystal structure of the N-terminal domain of the Human DEAD-BOX RNA helicase DDX5 (P68)

Summary for 4A4D

• Entry DOI: 10.2210/pdb4a4d/pdb
• Descriptor: PROBABLE ATP-DEPENDENT RNA HELICASE DDX5 (2 entities in total)
• Functional Keywords: atp-binding, hydrolase, rna-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus, nucleolus: P17844
• Total number of polymer chains: 1
• Total formula weight: 28702.96

Authors

Dutta, S.,Choi, Y.W.,Kotaka, M.,Fielding, B.C.,Tan, Y.J. (deposition date: 2011-10-11, release date: 2012-08-08, Last modification date: 2024-10-16)

Primary citation

Dutta, S.,Gupta, G.,Choi, Y.W.,Kotaka, M.,Fielding, B.C.,Song, J.,Tan, Y.J.
The Variable N-Terminal Region of Ddx5 Contains Structural Elements and Auto-Inhibits its Interaction with Ns5B of Hepatitis C Virus.
Biochem.J., 446:37-, 2012

PubMed 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 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 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.

PubMed: 22640416
DOI: 10.1042/BJ20120001

Experimental method

X-RAY DIFFRACTION (2.7 Å)