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Crystal structure of Dcp1p and its functional implications in mRNA decapping

Abstract

A major pathway of eukaryotic mRNA turnover begins with deadenylation, followed by decapping and 5′→3′ exonucleolytic degradation. A critical step in this pathway is decapping, which is carried out by an enzyme composed of Dcp1p and Dcp2p. The crystal structure of Dcp1p shows that it markedly resembles the EVH1 family of protein domains. Comparison of the proline-rich sequence (PRS)-binding sites in this family of proteins with Dcp1p indicates that it belongs to a novel class of EVH1 domains. Mapping of the sequence conservation on the molecular surface of Dcp1p reveals two prominent sites. One of these is required for the function of the Dcp1p–Dcp2p complex, and the other, corresponding to the PRS-binding site of EVH1 domains, is probably a binding site for decapping regulatory proteins. Moreover, a conserved hydrophobic patch is shown to be critical for decapping.

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Figure 1: Crystal structure of Dcp1p in comparison with EVH1 domains from Mena, Homer, N-WASP and RanBP.
Figure 2: Structure-based sequence alignments of Dcp1 proteins with the Mena EVH1 domain.
Figure 3: Molecular surface views of Dcp1p.
Figure 4: Biochemical analysis of mutations in conserved surface patches of Dcp1p.
Figure 5: Comparison of the potential ligand-binding sites of Dcp1p with those of EVH1 domains from Mena, Homer and N-WASP.

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Acknowledgements

We are grateful to the staffs at beamline BL41XU at SPRING-8, Japan for their support during data collection. This work is financially supported by the Agency for Science, Technology and Research (A*STAR) in Singapore (H.S.) and by the Howard Hughes Medical Institute (R.P.).

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Correspondence to Roy Parker or Haiwei Song.

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She, M., Decker, C., Sundramurthy, K. et al. Crystal structure of Dcp1p and its functional implications in mRNA decapping. Nat Struct Mol Biol 11, 249–256 (2004). https://doi.org/10.1038/nsmb730

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