Proteopedia

4brw

Crystal structure of the yeast Dhh1-Pat1 complexCrystal structure of the yeast Dhh1-Pat1 complex

Structural highlights

4brw is a 2 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.795Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DHH1_YEAST ATP-dependent RNA helicase involved in mRNA turnover, and more specifically in mRNA decapping by activating the decapping enzyme DCP1. Is involved in G1/S DNA-damage checkpoint recovery, probably through the regulation of the translational status of a subset of mRNAs. May also have a role in translation and mRNA nuclear export. Required for sporulation.[1] [2] [3] [4] [5] [6] [7] [8] [9]

Publication Abstract from PubMed

Translational repression and deadenylation of eukaryotic mRNAs result either in the sequestration of the transcripts in a nontranslatable pool or in their degradation. Removal of the 5' cap structure is a crucial step that commits deadenylated mRNAs to 5'-to-3' degradation. Pat1, Edc3 and the DEAD-box protein Dhh1 are evolutionary conserved factors known to participate in both translational repression and decapping, but their interplay is currently unclear. We report the 2.8 A resolution structure of yeast Dhh1 bound to the N-terminal domain of Pat1. The structure shows how Pat1 wraps around the C-terminal RecA domain of Dhh1, docking onto the Phe-Asp-Phe (FDF) binding site. The FDF-binding site of Dhh1 also recognizes Edc3, revealing why the binding of Pat1 and Edc3 on Dhh1 are mutually exclusive events. Using co-immunoprecipitation assays and structure-based mutants, we demonstrate that the mode of Dhh1-Pat1 recognition is conserved in humans. Pat1 and Edc3 also interfere and compete with the RNA-binding properties of Dhh1. Mapping the RNA-binding sites on Dhh1 with a crosslinking-mass spectrometry approach shows a large RNA-binding surface around the C-terminal RecA domain, including the FDF-binding pocket. The results suggest a model for how Dhh1-containing messenger ribonucleoprotein particles might be remodeled upon Pat1 and Edc3 binding.

Structural analysis of the yeast Dhh1-Pat1 complex reveals how Dhh1 engages Pat1, Edc3 and RNA in mutually exclusive interactions.,Sharif H, Ozgur S, Sharma K, Basquin C, Urlaub H, Conti E Nucleic Acids Res. 2013 Jul 12. PMID:23851565[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Hata H, Mitsui H, Liu H, Bai Y, Denis CL, Shimizu Y, Sakai A. Dhh1p, a putative RNA helicase, associates with the general transcription factors Pop2p and Ccr4p from Saccharomyces cerevisiae. Genetics. 1998 Feb;148(2):571-9. PMID:9504907
  2. ↑ Coller JM, Tucker M, Sheth U, Valencia-Sanchez MA, Parker R. The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes. RNA. 2001 Dec;7(12):1717-27. PMID:11780629
  3. ↑ Fischer N, Weis K. The DEAD box protein Dhh1 stimulates the decapping enzyme Dcp1. EMBO J. 2002 Jun 3;21(11):2788-97. PMID:12032091 doi:10.1093/emboj/21.11.2788
  4. ↑ Maillet L, Collart MA. Interaction between Not1p, a component of the Ccr4-not complex, a global regulator of transcription, and Dhh1p, a putative RNA helicase. J Biol Chem. 2002 Jan 25;277(4):2835-42. Epub 2001 Nov 5. PMID:11696541 doi:10.1074/jbc.M107979200
  5. ↑ Tseng-Rogenski SS, Chong JL, Thomas CB, Enomoto S, Berman J, Chang TH. Functional conservation of Dhh1p, a cytoplasmic DExD/H-box protein present in large complexes. Nucleic Acids Res. 2003 Sep 1;31(17):4995-5002. PMID:12930949
  6. ↑ Sheth U, Parker R. Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science. 2003 May 2;300(5620):805-8. PMID:12730603 doi:10.1126/science.1082320
  7. ↑ Bergkessel M, Reese JC. An essential role for the Saccharomyces cerevisiae DEAD-box helicase DHH1 in G1/S DNA-damage checkpoint recovery. Genetics. 2004 May;167(1):21-33. PMID:15166134
  8. ↑ Teixeira D, Sheth U, Valencia-Sanchez MA, Brengues M, Parker R. Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA. 2005 Apr;11(4):371-82. Epub 2005 Feb 9. PMID:15703442 doi:10.1261/rna.7258505
  9. ↑ Muhlrad D, Parker R. The yeast EDC1 mRNA undergoes deadenylation-independent decapping stimulated by Not2p, Not4p, and Not5p. EMBO J. 2005 Mar 9;24(5):1033-45. Epub 2005 Feb 10. PMID:15706350 doi:10.1038/sj.emboj.7600560
  10. ↑ Sharif H, Ozgur S, Sharma K, Basquin C, Urlaub H, Conti E. Structural analysis of the yeast Dhh1-Pat1 complex reveals how Dhh1 engages Pat1, Edc3 and RNA in mutually exclusive interactions. Nucleic Acids Res. 2013 Jul 12. PMID:23851565 doi:10.1093/nar/gkt600

4brw, resolution 2.79Å

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