A Sliding Docking Interaction Is Essential for Sequential and Processive Phosphorylation of an SR Protein by SRPK1

The 2.9 Å crystal structure of the core SRPK1:ASF/SF2 complex reveals that the N-terminal half of the basic RS domain of ASF/SF2, which is destined to be phosphorylated, is bound to an acidic docking groove of SRPK1 distal to the active site. Phosphorylation of ASF/SF2 at a single site in the C-term...

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Bibliographic Details
Published in:Molecular cell 2008-03, Vol.29 (5), p.563-576
Main Authors: Ngo, Jacky Chi Ki, Giang, Kayla, Chakrabarti, Sutapa, Ma, Chen-Ting, Huynh, Nhat, Hagopian, Jonathan C., Dorrestein, Pieter C., Fu, Xiang-Dong, Adams, Joseph A., Ghosh, Gourisankar
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Adenylyl Imidodiphosphate - chemistry
Adenylyl Imidodiphosphate - metabolism
Amino Acid Sequence
Animals
BASIC BIOLOGICAL SCIENCES
Binding Sites
CRYSTAL STRUCTURE
Crystallography, X-Ray
Humans
Mice
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes - metabolism
Nuclear Proteins - chemistry
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
PEPTIDES
PHOSPHORYLATION
Protein Binding
Protein Structure, Tertiary
Protein-Serine-Threonine Kinases - chemistry
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
PROTEINS
Ribonucleoside Diphosphate Reductase - chemistry
Ribonucleoside Diphosphate Reductase - genetics
Ribonucleoside Diphosphate Reductase - metabolism
RNA
RNA-Binding Proteins
Sequence Alignment
SERINE
Serine-Arginine Splicing Factors
SUBSTRATES
TRANSLOCATION
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Summary:The 2.9 Å crystal structure of the core SRPK1:ASF/SF2 complex reveals that the N-terminal half of the basic RS domain of ASF/SF2, which is destined to be phosphorylated, is bound to an acidic docking groove of SRPK1 distal to the active site. Phosphorylation of ASF/SF2 at a single site in the C-terminal end of the RS domain generates a primed phosphoserine that binds to a basic site in the kinase. Biochemical experiments support a directional sliding of the RS peptide through the docking groove to the active site during phosphorylation, which ends with the unfolding of a β strand of the RRM domain and binding of the unfolded region to the docking groove. We further suggest that the priming of the first serine facilitates directional substrate translocation and efficient phosphorylation.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2007.12.017