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Structure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis

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dc.abstract.enThe conserved decapping enzyme Dcp2 recognizes and removes the 5' eukaryotic cap from mRNA transcripts in a critical step of many cellular RNA decay pathways. Dcp2 is a dynamic enzyme that functions in concert with the essential activator Dcp1 and a diverse set of coactivators to selectively and efficiently decap target mRNAs in the cell. Here we present a 2.84 Å crystal structure of K. lactis Dcp1-Dcp2 in complex with coactivators Edc1 and Edc3, and with substrate analog bound to the Dcp2 active site. Our structure shows how Dcp2 recognizes cap substrate in the catalytically active conformation of the enzyme, and how coactivator Edc1 forms a three-way interface that bridges the domains of Dcp2 to consolidate the active conformation. Kinetic data reveal Dcp2 has selectivity for the first transcribed nucleotide during the catalytic step. The heterotetrameric Edc1-Dcp1-Dcp2-Edc3 structure shows how coactivators Edc1 and Edc3 can act simultaneously to activate decapping catalysis.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorZiemniak, Marcin
dc.contributor.authorTibble, Ryan W.
dc.contributor.authorMudridge, Joeffrey S.
dc.contributor.authorGross, John D.
dc.contributor.authorJemielity, Jacek
dc.date.accessioned2024-01-26T08:22:17Z
dc.date.available2024-01-26T08:22:17Z
dc.date.issued2018
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number1
dc.description.versionFINAL_PUBLISHED
dc.description.volume9
dc.identifier.doi10.1038/S41467-018-03536-X
dc.identifier.issn2041-1723
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/120938
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofNature Communications
dc.relation.pagesart.no. 1152
dc.rightsCC-BY
dc.sciencecloudnosend
dc.titleStructure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis
dc.typeJournalArticle
dspace.entity.typePublication