A divergent Sm fold in EDC3 proteins mediates DCP1 binding and P-body targeting.
Members of the (L)Sm (Sm and Sm-like) protein family are found across all kingdoms of life and play crucial roles in RNA metabolism. The P-body component EDC3 (enhancer of decapping 3) is a divergent member of this family that functions in mRNA decapping. EDC3 is composed of a N-terminal LSm domain, a central FDF domain, and a C-terminal YjeF-N domain. We show that this modular architecture enables EDC3 to interact with multiple components of the decapping machinery, including DCP1, DCP2, and Me31B. The LSm domain mediates DCP1 binding and P-body localization. We determined the three-dimensional structures of the LSm domains of Drosophila melanogaster and human EDC3 and show that the domain adopts a divergent Sm fold that lacks the characteristic N-terminal alpha-helix and has a disrupted beta4-strand. This domain remains monomeric in solution and lacks several features that canonical (L)Sm domains require for binding RNA. The structures also revealed a conserved patch of surface residues that are required for the interaction with DCP1 but not for P-body localization. The conservation of surface and of critical structural residues indicates that LSm domains in EDC3 proteins adopt a similar fold that has separable novel functions that are absent in canonical (L)Sm proteins.
Tritschler
Felix
F
Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany.
Eulalio
Ana
A
Truffault
Vincent
V
Hartmann
Marcus D
MD
Helms
Sigrun
S
Schmidt
Steffen
S
Coles
Murray
M
Izaurralde
Elisa
E
Weichenrieder
Oliver
O
D000818:Animals; D020169:Caspases; D022082:Cellular Structures / Q000378:metabolism*; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*
D029721:Drosophila Proteins; C525042:EDC3 protein, human; C525041:Edc3 protein, Drosophila; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D020169:Caspases; C103568:Dcp-1 protein, Drosophila