RRC ID 17448
Author Fromm SA, Truffault V, Kamenz J, Braun JE, Hoffmann NA, Izaurralde E, Sprangers R.
Title The structural basis of Edc3- and Scd6-mediated activation of the Dcp1:Dcp2 mRNA decapping complex.
Journal EMBO J
Abstract The Dcp1:Dcp2 decapping complex catalyses the removal of the mRNA 5' cap structure. Activator proteins, including Edc3 (enhancer of decapping 3), modulate its activity. Here, we solved the structure of the yeast Edc3 LSm domain in complex with a short helical leucine-rich motif (HLM) from Dcp2. The motif interacts with the monomeric Edc3 LSm domain in an unprecedented manner and recognizes a noncanonical binding surface. Based on the structure, we identified additional HLMs in the disordered C-terminal extension of Dcp2 that can interact with Edc3. Moreover, the LSm domain of the Edc3-related protein Scd6 competes with Edc3 for the interaction with these HLMs. We show that both Edc3 and Scd6 stimulate decapping in vitro, presumably by preventing the Dcp1:Dcp2 complex from adopting an inactive conformation. In addition, we show that the C-terminal HLMs in Dcp2 are necessary for the localization of the Dcp1:Dcp2 decapping complex to P-bodies in vivo. Unexpectedly, in contrast to yeast, in metazoans the HLM is found in Dcp1, suggesting that details underlying the regulation of mRNA decapping changed throughout evolution.
Volume 31(2)
Pages 279-90
Published 2012-1-18
DOI 10.1038/emboj.2011.408
PII emboj2011408
PMID 22085934
PMC PMC3261563
MeSH Amino Acid Motifs Amino Acid Sequence Animals Drosophila melanogaster / genetics Evolution, Molecular Gene Expression Regulation, Fungal* Models, Molecular Molecular Sequence Data Multiprotein Complexes Nuclear Magnetic Resonance, Biomolecular Protein Conformation Protein Interaction Mapping Protein Structure, Tertiary RNA Caps / genetics RNA Caps / metabolism* RNA, Fungal / genetics RNA, Fungal / metabolism* RNA, Messenger / genetics RNA, Messenger / metabolism* Schizosaccharomyces / genetics Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / chemistry* Schizosaccharomyces pombe Proteins / metabolism Schizosaccharomyces pombe Proteins / physiology Sequence Alignment Sequence Homology, Amino Acid Structure-Activity Relationship
IF 9.889
Times Cited 67
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Yeast FY21463(RS002) FY21464(RS003) FY21469(RS008) FY21472(RS011) FY21462(RS001) FY21474(RS013) FY21467(RS006) FY21470(RS009) FY21477(RS016) FY21475(RS014) FY21468(RS007) FY21471(RS010) FY21476(RS015) FY21473(RS012) FY21466(RS005) FY21465(RS004)