Reference - PMID:27694842 - Structural basis of mRNA-cap recognition by Dcp1-Dcp2.
Reference summary
- PubMed ID
- PMID:27694842
- Title
- Structural basis of mRNA-cap recognition by Dcp1-Dcp2.
- Authors
- Mugridge JS, Ziemniak M, Jemielity J, Gross JD
- Citation
- Nat Struct Mol Biol 2016 Nov;23(11):987-994
- Publication year
- 2016
- Abstract
- 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-Å-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.
