Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Struct Mol Biol. 2010 Sep;17(9):1096-101. doi: 10.1038/nsmb.1879. Epub 2010 Aug 15.

A split active site couples cap recognition by Dcp2 to activation.

Author information

  • 1Graduate Group in Biophysics, University of California, San Francisco, California, USA.

Abstract

Decapping by Dcp2 is an essential step in 5'-to-3' mRNA decay. In yeast, decapping requires an open-to-closed transition in Dcp2, though the link between closure and catalysis remains elusive. Here we show using NMR that cap binds conserved residues on both the catalytic and regulatory domains of Dcp2. Lesions in the cap-binding site on the regulatory domain reduce the catalytic step by two orders of magnitude and block the formation of the closed state, whereas Dcp1 enhances the catalytic step by a factor of 10 and promotes closure. We conclude that closure occurs during the rate-limiting catalytic step of decapping, juxtaposing the cap-binding region of each domain to form a composite active site. This work suggests a model for regulation of decapping where coactivators trigger decapping by stabilizing a labile composite active site.

PMID:
20711189
[PubMed - indexed for MEDLINE]
PMCID:
PMC2933276
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk