Structural basis of dcp2 recognition and activation by dcp1.
A critical step in mRNA degradation is the removal of the 5' cap structure, which is catalyzed by the Dcp1-Dcp2 complex. The crystal structure of an S. pombe Dcp1p-Dcp2n complex combined with small-angle X-ray scattering analysis (SAXS) reveals that Dcp2p exists in open and closed conformations, with the closed complex being, or closely resembling, the catalytically more active form. This suggests that a conformational change between these open and closed complexes might control decapping. A bipartite RNA-binding channel containing the catalytic site and Box B motif is identified with a bound ATP located in the catalytic pocket in the closed complex, suggesting possible interactions that facilitate substrate binding. Dcp1 stimulates the activity of Dcp2 by promoting and/or stabilizing the closed complex. Notably, the interface of Dcp1 and Dcp2 is not fully conserved, explaining why the Dcp1-Dcp2 interaction in higher eukaryotes requires an additional factor.
She
Meipei
M
Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Proteos, 138673 Singapore.
Decker
Carolyn J
CJ
Svergun
Dmitri I
DI
Round
Adam
A
Chen
Nan
N
Muhlrad
Denise
D
Parker
Roy
R
Song
Haiwei
H
D000255:Adenosine Triphosphate / Q000737:chemistry; D000409:Alanine / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005982:Glutathione Transferase / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D040681:Structural Homology, Protein
C527678:Dcp1 protein, S pombe; C508496:Dcp2 protein, S pombe; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D000255:Adenosine Triphosphate; D005982:Glutathione Transferase; D000409:Alanine