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Human DEAD-box RNA-helicase DDX47, conserved domain I in complex with AMP

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PDB Code 3BER Target Class ATPases Target DDX47 Alias DDX47, DKFZp564O176, E4-DBP, FLJ30012, HQ0256, MSTP162 Disease Area/Function cancer Date Deposited Nov 20 2007 Authors T.KARLBERG, R.D.BUSAM, C.H.ARROWSMITH, H.BERGLUND, R.COLLINS, L.G.DAHLGREN, A.EDWARDS, S.FLODIN, A.FLORES, S.GRASLUND, M.HAMMARSTROM, I.JOHANSSON, A.KALLAS, T.KOTENYOVA, L.LEHTIO, M.MOCHE, M.E.NILSSON, P.NORDLUND, T.NYMAN, C.PERSSON, J.SAGEMARK, L.SVENSSON, A.G.THORSELL, L.TRESAUGUES, S.VAN DEN BERG, J.WEIGELT, M.WELIN, L.HOLMBERG-SCHIAVONE

About this structure

The ATP-dependent DEAD-box RNA helicase DDX47 (DEAD box protein 47, EC: 3.6.1.-) belongs to the DExD/H RNA-binding helicase family of proteins that are involved in all aspects of cellular RNA-metabolism such as transcription, splicing, RNA transport, translation and ribosome biogenesis. All proteins in this family are supposed to bind and hydrolyze trinucleotides, mainly ATP, and are believed to function as RNA chaperones that bind RNA and assist in unwinding of RNA secondary structure or folding of RNA complexes. Members of this family normally consist of two domains: an N-terminal domain with the conserved DExD/H motif and a C-terminal helicase domain (Cordin et al. 2006).

DDX47 has been linked to the nucleolar protein NOP132 and hence localized to the nucleolus where it is hypothesized to be involved in the processing of rRNA (Sekiguchi et al. 2006). Further, DDX47 has been identified as a binding partner to the GABAA receptor-associated protein (GABARAP). Co-transfection of GABARAP and DDX47 cDNA into a tumor cell line has induced apoptosis (Lee et al. 2005).

We have determined the three-dimensional structure of the conserved domain 1 (DEAD-domain) of human DDX47 to a resolution of 1.4 Å. The structure was solved with the MR (molecular replacement) method using HERA N-terminal domain as a search template (PDB: 2GXS). The protein’s fold resembles an α-β RecA-like domain. Curiously enough, AMP was observed in the electron density, very clearly, despite the fact that ADP and MgCl2 had been added during purification and to the crystallization drops.

References

  1. Lee J.H., Rho S.B. and Chun T. (2005) GABAA receptor-associated protein (GABARAP) induces apoptosis by interacting with DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 47 (DDX 47). Biotechnology Letters 27: 623-628.
  2. Cordin O., Banroques J., Tanner N.K., and Linder P. (2006) The DEAD-box protein family of RNA helicases. Gene 367: 17-37.
  3. Sekiguchi T., Hayano T., Yanagida M., Takahashi N. and Nishimoto T. (2006) NOP132 is required for proper nucleolus localization of DEAD-box RNA helicase DDX47. Nucleic Acids Research 34: 4593-4608.