PDBsum entry 1f8a

Isomerase

PDB id: 1f8a

Contents

Protein chain

155 a.a. *

Ligands

TYR-SEP-PRO-THR-SEP-PRO-SER

Waters ×152

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structural basis for phosphoserine-Proline recognition by group IV ww domains.

Authors

M.A.Verdecia, M.E.Bowman, K.P.Lu, T.Hunter, J.P.Noel.

Ref.

Nat Struct Biol, 2000, 7, 639-643. [DOI no: 10.1038/77929]

PubMed id

10932246

Abstract

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.

Figure 1.
Figure 1. Overall architecture of human Pin1. a, Ribbon representation of the Pin1 -CTD peptide complex. Residues 1 -5 of Pin1 are visible in the electron density maps but not shown here for clarity; residues 39 -50 are disordered. Apostrophes distinguish the WW domain colored purple from the PPIase domain colored blue. The CTD peptide backbone is yellow. Residues of the CTD peptide are labeled with primes. Atoms are colored according to type: carbon, light gray; nitrogen, blue; phosphorus, black; oxygen, red; sulfur, yellow. Dotted green lines depict hydrogen bonds. b, Ribbon representation of the Pin1 -PEG complex19. c, Stereo view of the SIGMAA weighted |2F[o] - F[c]| electron density map contoured at 1.0 around the Tyr 23-Trp 34 clamp.

Figure 2.
Figure 2. The Pin1 -CTD peptide binding interface. a, Ribbon diagram of the Pin1 WW domain bound to Tyr-P.Ser-Pro-Thr-P.Ser-Pro-Ser depicted after a 90° rotation around a vertical axis from the view shown in Fig. 1a. This view is looking onto the concave WW domain peptide binding surface opposite the PPIase domain. The carbon atoms of the CTD peptide are colored gold to distinguish them from the WW domain side chain atoms. The water molecule mediating Tyr 23 -phosphate contacts is shown as a cyan sphere. Hydrogen bonds are shown as green dotted spheres. b, Molecular surface representation of the WW domain -peptide interface rendered after a slight rotation around the vertical axis from the view depicted in (a). The solvent accessible surface for the Pin1 WW domain residues was calculated in GRASP33, and the acidic and basic residues colored red and blue, respectively. c, Schematic and energetic view of the Pin1 -phosphopeptide complex. Pin1 residues are purple and CTD residues black. Residues participating in van der Waals contacts are highlighted with gold and the extended van der Waals surfaces appear as dotted gold curves. Hydrogen bonds are shown as dashed green lines. In the case of the S16H and W34H mutants, some of the apparent binding is likely being contributed by the PPIase domain. Residues are given in the single letter code. Values in parentheses represent deviations from theoretical binding isotherms.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 639-643) copyright 2000.