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The Prp19 WD40 domain contains a conserved protein interaction region essential for its function.

Prp19 is a member of the WD40 repeat family of E3 ubiquitin ligases and a conserved eukaryotic RNA splicing factor essential for activation and stabilization of the spliceosome. To understand the role of the WD40 repeat domain of Prp19 we have determined its structure using X-ray crystallography. The domain has a distorted seven bladed WD40 architecture with significant asymmetry due to irregular packing of blades one and seven into the core of the WD40 domain. Structure-based mutagenesis identified a highly conserved surface centered around blade five that is required for the physical interaction between Prp19 and Cwc2, another essential splicing factor. This region is found to be required for Prp19 function and yeast viability. Experiments in vitro and in vivo demonstrate that two molecules of Cwc2 bind to the Prp19 tetramer. These coupled structural and functional studies provide a model for the functional architecture of Prp19.

Pubmed ID: 20462492 RIS Download

Mesh terms: Amino Acid Motifs | Crystallography, X-Ray | Eukaryota | Mutagenesis | Protein Structure, Tertiary | Proteins | RNA Splicing | Saccharomyces cerevisiae | Spliceosomes | Ubiquitin-Protein Ligases | X-Rays

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Associated grants

  • Agency: NCRR NIH HHS, Id: P20RR020171
  • Agency: NIGMS NIH HHS, Id: T32 GM008320
  • Agency: NCRR NIH HHS, Id: P20 RR020171
  • Agency: NIH HHS, Id: DP2 OD004483-01
  • Agency: NCRR NIH HHS, Id: P20 RR020171-066669
  • Agency: NIH HHS, Id: 1DP2OD004483
  • Agency: Howard Hughes Medical Institute, Id: R01 GM075156-05
  • Agency: NIGMS NIH HHS, Id: T32GM08320
  • Agency: NIGMS NIH HHS, Id: R01 GM075156
  • Agency: NIGMS NIH HHS, Id: R01GM075156
  • Agency: NIGMS NIH HHS, Id: DP2 OD004483
  • Agency: NIH HHS, Id:

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