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Published on: July 14, 2015
Structural basis for phosphoserine-proline recognition by group IV WW domains
M A Verdecia1, M E Bowman, K P Lu
1Structural Biology Laboratory, University of California, San Diego, La Jolla, California 92093, USA.
Pin1
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Pin1 protein contains WW and peptidyl-prolyl cis-trans isomerase (PPIase) domains.
- WW domains recognize phosphoserine (P.Ser)/phosphothreonine (P.Thr)-proline motifs.
- Understanding Pin1's recognition mechanism is crucial for its biological roles.
Purpose of the Study:
- To investigate the energetic and structural basis of Pin1's WW domain binding to phosphopeptides.
- To elucidate the specific interactions involved in recognizing phosphoserine and proline residues.
Main Methods:
- X-ray crystallography was used to determine the structure of the Pin1-phosphopeptide complex.
- Energetic analysis was performed to quantify binding interactions.
Main Results:
- The crystal structure revealed Pin1 bound to a doubly phosphorylated peptide derived from RNA polymerase II CTD.
- Specific residues in Pin1, including Arg and Ser side chains and backbone amides, were identified as key for P.Ser recognition.
- The structure detailed the interactions with proline rings and the peptide backbone.
Conclusions:
- Pin1 recognizes P.Ser-Pro motifs through a combination of side chain and backbone interactions.
- The observed P.Ser recognition mechanism by Pin1's WW domain may not be conserved across all WW domains due to variable residue conservation.
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