5j3q
From Proteopedia
Crystal structure of S. pombe Dcp1:Edc1 mRNA decapping complex
Structural highlights
Function[DCP1_SCHPO] Component of the decapping complex necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP. Decapping is the major pathway of mRNA degradation in yeast. It occurs through deadenylation, decapping and subsequent 5' to 3' exonucleolytic decay of the transcript body.[1] Publication Abstract from PubMedThe removal of the mRNA 5' cap (decapping) by Dcp2 shuts down translation and commits mRNA to full degradation. Dcp2 activity is enhanced by activator proteins such as Dcp1 and Edc1. However, owing to conformational flexibility, the active conformation of Dcp2 and the mechanism of decapping activation have remained unknown. Here, we report a 1.6-A-resolution crystal structure of the Schizosaccharomyces pombe Dcp2-Dcp1 heterodimer in an unprecedented conformation that is tied together by an intrinsically disordered peptide from Edc1. In this ternary complex, an unforeseen rotation of the Dcp2 catalytic domain allows residues from both Dcp2 and Dcp1 to cooperate in RNA binding, thus explaining decapping activation by increased substrate affinity. The architecture of the Dcp2-Dcp1-Edc1 complex provides a rationale for the conservation of a sequence motif in Edc1 that is also present in unrelated decapping activators, thus indicating that the presently described mechanism of decapping activation is evolutionarily conserved. Structure of the Dcp2-Dcp1 mRNA-decapping complex in the activated conformation.,Valkov E, Muthukumar S, Chang CT, Jonas S, Weichenrieder O, Izaurralde E Nat Struct Mol Biol. 2016 May 16. doi: 10.1038/nsmb.3232. PMID:27183195[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Chang, C T | Izaurralde, E | Jonas, S | Muthukumar, S | Valkov, E | Weichenrieder, O | Decapping | Evh1 | Hydrolase | Mrna decay
