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 PubMed
Removal 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
- ↑ Sakuno T, Araki Y, Ohya Y, Kofuji S, Takahashi S, Hoshino S, Katada T. Decapping reaction of mRNA requires Dcp1 in fission yeast: its characterization in different species from yeast to human. J Biochem. 2004 Dec;136(6):805-12. PMID:15671491 doi:http://dx.doi.org/136/6/805
- ↑ Mugridge JS, Ziemniak M, Jemielity J, Gross JD. Structural basis of mRNA-cap recognition by Dcp1-Dcp2. Nat Struct Mol Biol. 2016 Oct 3. doi: 10.1038/nsmb.3301. PMID:27694842 doi:http://dx.doi.org/10.1038/nsmb.3301
