Structural Basis for Phosphoserine-Proline Recognition by Group IV WW Domains

Nat Struct Biol. 2000 Aug;7(8):639-43. doi: 10.1038/77929.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Fluorescence Polarization
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptidylprolyl Isomerase / chemistry*
  • Peptidylprolyl Isomerase / metabolism*
  • Phosphopeptides / chemistry
  • Phosphopeptides / metabolism
  • Phosphoserine / metabolism*
  • Proline / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thermodynamics
  • Tryptophan / metabolism*

Substances

  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptide Fragments
  • Phosphopeptides
  • Recombinant Fusion Proteins
  • Phosphoserine
  • Tryptophan
  • Proline
  • RNA Polymerase II
  • PIN1 protein, human
  • Peptidylprolyl Isomerase

Associated data

  • PDB/1F8A