2wx3
Asymmetric trimer of the human DCP1a C-terminal domain
Structural highlights
FunctionDCP1A_HUMAN 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. Contributes to the transactivation of target genes after stimulation by TGFB1.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDCP1 stimulates the decapping enzyme DCP2, which removes the mRNA 5' cap structure committing mRNAs to degradation. In multicellular eukaryotes, DCP1-DCP2 interaction is stabilized by additional proteins, including EDC4. However, most information on DCP2 activation stems from studies in S. cerevisiae, which lacks EDC4. Furthermore, DCP1 orthologs from multicellular eukaryotes have a C-terminal extension, absent in fungi. Here, we show that in metazoa, a conserved DCP1 C-terminal domain drives DCP1 trimerization. Crystal structures of the DCP1-trimerization domain reveal an antiparallel assembly comprised of three kinked alpha-helices. Trimerization is required for DCP1 to be incorporated into active decapping complexes and for efficient mRNA decapping in vivo. Our results reveal an unexpected connectivity and complexity of the mRNA decapping network in multicellular eukaryotes, which likely enhances opportunities for regulating mRNA degradation. DCP1 forms asymmetric trimers to assemble into active mRNA decapping complexes in metazoa.,Tritschler F, Braun JE, Motz C, Igreja C, Haas G, Truffault V, Izaurralde E, Weichenrieder O Proc Natl Acad Sci U S A. 2009 Dec 4. PMID:19966221[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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