Abstract of the PDB Structure's related Publication:
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.
The Dcp2 protein removes the cap structure of mRNA by cleaving capped mRNA which allows initiating 5′ to 3′ degradation. Decapping holoenzyme is composed of the catalytic Dcp2 subunit and the coactivator Dcp1. Dcp1 and the substrate RNA promote the closed form of the enzyme and the catalytic step of decapping is rate limiting and accelerated by Dcp1.