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Human DEAD box RNA helicase DDX19 (Dbp5)

PDB Code 3G0H Target Class ATPases Target DDX19 Alias DBP5, DDX19, DDX19B, RNAh Disease Area/Function cancer Date Deposited Jan 28 2009 Authors T.KARLBERG, L.LEHTIO, R.COLLINS, C.H.ARROWSMITH, H.BERGLUND, C.BOUNTRA, L.G.DAHLGREN, A.M.EDWARDS, S.FLODIN, A.FLORES, S.GRASLUND, M.HAMMARSTROM, A.JOHANSSON, I.JOHANSSON, T.KOTENYOVA, M.MOCHE, M.E.NILSSON, P.NORDLUND, T.NYMAN, C.PERSSON, J.SAGEMARK, P.SCHUTZ, M.I.SIPONEN, A.G.THORSELL, L.TRESAUGUES, S.VAN DEN BERG, J.WEIGELT, M.WELIN, M.WISNIEWSKA, H.SCHULER Related Structure 3EWS

About this structure

The DExD/H family of RNA-binding helicases consists of a large group of proteins involved in general cellular RNA-metabolism such as transcription, splicing, RNA nucleocytoplasmatic transport, translation and ribosome biogenesis (1). All DExD/H helicases bind and hydrolyze ATP, and are believed to unwind RNA-secondary structure or assist in the folding of RNA/RNP complexes thus acting as RNA chaperones. Proteins in this family normally consist of two domains: an N-terminal domain with the conserved DExD/H motif and a C-terminal helicase domain. There are at least eight conserved motifs that are involved in coordination and hydrolysis of ATP and binding of RNA (2,3).

DDX19 is a human DEAD-box helicase that is required for mRNA export through the nuclear pore complex (4). Its yeast ortholog, Dbp5 (5), associates with nascent mRNA already in the nucleus. Previously, we solved the structure of DDX19, containing the DEAD-domain and the helicase domain in complex with ADP, at 2.7 Å resolution (3EWS). Now, DDX19 in complex with MgADPNP and RNA (a decauracil mRNA mimic) has been solved to 2.7Å resolution. DDX19 has the typical DEAD-box helicase fold with two α-β RecA-like domains connected via a flexible linker. The nucleotide binding site is located in a pocket between the two domains. The structure shows that both domains contribute to nucleotide and RNA binding. Six bases of the RNA molecule are visible in the electron density, positioned across the top of the cleft. As in previous helicase complexes, DDX19 introduces a kink in the RNA molecule, but unlike the previous structures, the two bases downstream of the kink do not stack with each other.

Comparing the two DDX19 structures (with and without RNA bound) shows that an α-helical segment of the N-terminal flanking region is wedged between the core domains in the RNA-free protein. This helix prevents cleft closure and positions the N-terminal flanking sequence in the RNA binding cleft, or in its proximity. In the ADPNP-RNA ternary complex, this α-helix has moved out to allow formation of the closed state, enabling RNA binding and nucleotide hydrolysis.

References

  1. Linder, P. (2006) Dead-box proteins: a family affair: active and passive players in RNP-remodeling. Nucleic Acids Res. 34:4168-80.
  2. Cordin, O., Banroques, J., et al. (2006) The DEAD-box protein family of RNA helicases. Gene 367: 17-37.
  3. Pyle, A.M. (2008) Translocation and unwinding mechanisms of RNA and DNA helicase. Annu. Rev. Biophys. 37:317-36.
  4. Schmitt, C., von Kobbe, C. et al. (1999) Dbp5, a DEAD-box protein required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN/Nup159p. EMBO J. 18:4332-47.
  5. Snay-Hodge, C.A., Colot, H.V., Goldstein, A.L. & Cole, C.N. (1998) EMBO J. 17, 2663-2676.