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Crystal Structure Analysis of the RNA Helicase DHX9

PDB Code 3LLM Target Class DExD-DExH RNA helicases Target DHX9 Alias DDX9, DHX9, LKP, NDHII, RHA Disease Area/Function cancer Date Deposited Jan 29 2010 Authors P.SCHUTZ, T.KARLBERG, C.H.ARROWSMITH, H.BERGLUND, C.BOUNTRA, R.COLLINS, A.M.EDWARDS, S.FLODIN, A.FLORES, S.GRASLUND, M.HAMMARSTROM, I.JOHANSSON, A.KALLAS, T.KOTENYOVA, P.KRAULIS, M.MOCHE, T. NIELSEN, P.NORDLUND, T.NYMAN, C.PERSSON, M.I.SIPONEN, L.SVENSSON, A.G.THORSELL, L.TRESAUGUES, S.VAN DEN BERG, J.WEIGELT, M.WELIN, M.WISNIEWSKA, H.SCHULER

About this structure

DHX9 (also known as RNA helicase A, or maleless) binds ssRNA and ssDNA, and unwinds double stranded nucleic acids. The energy for the unwinding comes from the hydrolysis of ATP, GTP, CTP or UTP.(1-2). DHX9 interacts with a wide range of proteins, for example:

  1. It mediates association of CREB-binding protein (CBP) with RNA polymerase-II (PolII)(3)
  2. It acts as an RNA loading factor in the RNA-induced silencing complex.(4)
  3. It binds several transcription regulators.(5)

It is involved regulation of transcription and translation of specific cellular and retroviral mRNAs.(6-7) Therefore, it links regulation of transcription and translation of these mRNAs. Understanding of the DHX9 function is of medical importance because of its role in the replication of various viruses such as HIV and hepatitis C virus.(8)-(9)

The crystal structure shows DHX9 residues 325-563 in complex with of ADP and Mn2+.

References

  1. Lee, C. G., and Hurwitz, J. (1992) A new RNA helicase isolated from HeLa cells that catalytically translocates in the 3' to 5' direction, J Biol Chem 267, 4398-4407. PubMed 1537828
  2. Huang, M., and Mitchell, B. S. (2008) Guanine nucleotide depletion mediates translocation of nucleolar proteins, including RNA helicase A (DHX-9), Nucleosides Nucleotides Nucleic Acids 27, 704-711. PubMed 18600529
  3. Nakajima, T., Uchida, C., Anderson, S. F., Lee, C. G., Hurwitz, J., Parvin, J. D., and Montminy, M. (1997) RNA helicase A mediates association of CBP with RNA polymerase II, Cell 90, 1107-1112. PubMed 9323138
  4. Robb, G. B., and Rana, T. M. (2007) RNA helicase A interacts with RISC in human cells and functions in RISC loading, Mol Cell 26, 523-537. PubMed 17531811
  5. Fuller-Pace, F. V. (2006) DExD/H box RNA helicases: multifunctional proteins with important roles in transcriptional regulation, Nucleic Acids Res 34, 4206-4215. PubMed 16935882
  6. Tettweiler, G., and Lasko, P. (2006) A new model for translational regulation of specific mRNAs, Trends Biochem Sci 31, 607-610. PubMed 17015016
  7. Hartman, T. R., Qian, S., Bolinger, C., Fernandez, S., Schoenberg, D. R., and Boris-Lawrie, K. (2006) RNA helicase A is necessary for translation of selected messenger RNAs, Nat Struct Mol Biol 13, 509-516. PubMed 16680162
  8. Tang, H., Gaietta, G. M., Fischer, W. H., Ellisman, M. H., and Wong-Staal, F. (1997) A cellular cofactor for the constitutive transport element of type D retrovirus, Science 276, 1412-1415. PubMed 9162007
  9. Isken, O., Grassmann, C. W., Sarisky, R. T., Kann, M., Zhang, S., Grosse, F., Kao, P. N., and Behrens, S. E. (2003) Members of the NF90/NFAR protein group are involved in the life cycle of a positive-strand RNA virus, EMBO J 22, 5655-5665. PubMed 14592965