Structural basis for phosphoserine-proline recognition by group IV WW domains.
Pin1 contains an N-terminal WW domain and a C-terminal peptidyl-prolyl cis-trans isomerase (PPIase) domain connected by a flexible linker. To address the energetic and structural basis for WW domain recognition of phosphoserine (P.Ser)/phosphothreonine (P. Thr)- proline containing proteins, we report the energetic and structural analysis of a Pin1-phosphopeptide complex. The X-ray crystal structure of Pin1 bound to a doubly phosphorylated peptide (Tyr-P.Ser-Pro-Thr-P.Ser-Pro-Ser) representing a heptad repeat of the RNA polymerase II large subunit's C-terminal domain (CTD), reveals the residues involved in the recognition of a single P.Ser side chain, the rings of two prolines, and the backbone of the CTD peptide. The side chains of neighboring Arg and Ser residues along with a backbone amide contribute to recognition of P.Ser. The lack of widespread conservation of the Arg and Ser residues responsible for P.Ser recognition in the WW domain family suggests that only a subset of WW domains can bind P.Ser-Pro in a similar fashion to that of Pin1.
Structural Biology Laboratory, University of California, San Diego, La Jolla, California 92093, USA.
M A
MA
Verdecia
M E
ME
Bowman
K P
KP
Lu
T
T
Hunter
J P
JP
Noel
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005454:Fluorescence Polarization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000378:metabolism*; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D010768:Phosphoserine / Q000378:metabolism*; D011392:Proline / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013816:Thermodynamics; D014364:Tryptophan / Q000378:metabolism*
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010446:Peptide Fragments; D010748:Phosphopeptides; D011993:Recombinant Fusion Proteins; D010768:Phosphoserine; D014364:Tryptophan; D011392:Proline; D012319:RNA Polymerase II; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase