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Human DEAD-box RNA-helicase DDX19 in complex with ADP

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PDB Code 3EWS Target Class ATPases Target DDX19 Alias DBP5, DDX19, DDX19B, RNAh Disease Area/Function cancer Date Deposited Oct 16 2008 Authors LEHTIO, L., KARLBERG, T., ANDERSSON, J., ARROWSMITH, C.H., BERGLUND, H., BOUNTRA, C., COLLINS, R., DAHLGREN, L.G., EDWARDS, A.M., FLODIN, S., FLORES, A., GRASLUND, S., HAMMARSTROM, M., JOHANSSON, A., JOHANSSON, I., KOTENYOVA, T., MOCHE, M., NILSSON, M.E., NORDLUND, P., NYMAN, T., OLESEN, K., PERSSON, C., SAGEMARK, J., THORSELL, A.G., TRESAUGUES, L., VAN DEN BERG, S., WEIGELT, J., WELIN, M., WIKSTROM, M., WISNIEWSKA, M., SCHUELER, H. Related Structure 3G0H

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, based on primary sequence alignments that are involved in coordination and hydrolysis of ATP and binding of RNA (2,3).

DDX19 (or Dbp5) is a human DEAD-box helicase that is required for mRNA export from the nucleus (4). DDX19 is located primarily in the cytosol, but is recruited to the nuclear pore complex, where it assists in the mRNA export. Futher, the helicase is involved in translation termination and interacts with release factors eRF1 and eRF3 (5).

We have solved the structure of the conserved core of DDX19, containing the DEAD-domain and the helicase domain in complex with ADP, at 2.7 Å resolution. DDX19 has a fold that is typical of a DEAD-box helicase 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. ATP hydrolysis at this site enables DDX19 to translocate along ssRNA and remove paired strands or proteins (3).

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. Gross, T., Siepmann, A., et al. (2007) The DEAD-Box RNA helicase Dbp5 functions in translation termination. Science 315:646-649.