5KQ4

Crystal structure of S. pombe Dcp1/Dcp2 in complex with H. sapiens PNRC2 and synthetic cap analog

Summary for 5KQ4

• Entry DOI: 10.2210/pdb5kq4/pdb
• Related: 5KQ1
• Descriptor: mRNA-decapping enzyme subunit 1, Proline-rich nuclear receptor coactivator 2, mRNA decapping complex subunit 2, ... (5 entities in total)
• Functional Keywords: decapping mrna decay nudix cap analog, hydrolase
• Biological source: Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast); More
• Total number of polymer chains: 6
• Total formula weight: 97154.38

Authors

Mugridge, J.S.,Ziemniak, M.,Jemielity, J.,Gross, J.D. (deposition date: 2016-07-05, release date: 2016-10-05, Last modification date: 2023-10-04)

Primary citation

Mugridge, J.S.,Ziemniak, M.,Jemielity, J.,Gross, J.D.
Structural basis of mRNA-cap recognition by Dcp1-Dcp2.
Nat.Struct.Mol.Biol., 23:987-994, 2016

PubMed 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.

PubMed: 27694842
DOI: 10.1038/nsmb.3301

Experimental method

X-RAY DIFFRACTION (2.56 Å)