5kq4
From Proteopedia
Crystal structure of S. pombe Dcp1/Dcp2 in complex with H. sapiens PNRC2 and synthetic cap analog
Structural highlights
FunctionDCP1_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 PubMedRemoval of the 5' cap on mRNA by the decapping enzyme Dcp2 is a critical step in 5'-to-3' mRNA decay. Understanding the structural basis of Dcp2 activity has been a challenge because Dcp2 is dynamic and has weak affinity for the cap substrate. Here we present a 2.6-A-resolution crystal structure of a heterotrimer of fission yeast Dcp2, its essential activator Dcp1, and the human NMD cofactor PNRC2, in complex with a tight-binding cap analog. Cap binding is accompanied by a conformational change in Dcp2, thereby forming a composite nucleotide-binding site comprising conserved residues in the catalytic and regulatory domains. Kinetic analysis of PNRC2 revealed that a conserved short linear motif enhances both substrate affinity and the catalytic step of decapping. These findings explain why Dcp2 requires a conformational change for efficient catalysis and reveals that coactivators promote RNA binding and the catalytic step of decapping, possibly through different conformational states. Structural basis of mRNA-cap recognition by Dcp1-Dcp2.,Mugridge JS, Ziemniak M, Jemielity J, Gross JD Nat Struct Mol Biol. 2016 Oct 3. doi: 10.1038/nsmb.3301. PMID:27694842[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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