The peptidyl prolyl cis/trans-isomerase Pin1 recognizes the phospho-Thr212-Pro213 site on Tau

Biochemistry. 2004 Feb 24;43(7):2032-40. doi: 10.1021/bi035479x.

Abstract

The interaction between the neuronal Tau protein and the Pin1 prolyl cis/trans-isomerase is dependent on the phosphorylation state of the former. The interaction site was mapped to the unique phospho-Thr231-Pro232 motif, despite the presence of many other Thr/Ser-Pro phosphorylation sites in Tau and structural evidence that the interaction site does not significantly extend beyond those very two residues. We demonstrate here by NMR and fluorescence mapping that the Alzheimer's disease specific epitope centered around the phospho-Thr212-Pro213 motif is also an interaction site, and that the sole phospho-Thr-Pro motif is already sufficient for interaction. Because a detectable fraction of the Pro213 amide bond in the peptide centered around the phospho-Thr212-Pro213 motif is in the cis conformation, catalysis of the isomerization by the catalytic domain of Pin1 could be investigated via NMR spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Catalytic Domain
  • Dipeptides / chemistry
  • Dipeptides / metabolism
  • Epitope Mapping
  • Humans
  • Molecular Sequence Data
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptidylprolyl Isomerase / chemistry*
  • Peptidylprolyl Isomerase / metabolism*
  • Phosphorylation
  • Phosphothreonine / chemistry
  • Phosphothreonine / metabolism*
  • Proline / chemistry
  • Proline / metabolism*
  • Protein Interaction Mapping
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • tau Proteins / chemistry*
  • tau Proteins / metabolism*

Substances

  • Dipeptides
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Recombinant Fusion Proteins
  • tau Proteins
  • Phosphothreonine
  • Proline
  • PIN1 protein, human
  • Peptidylprolyl Isomerase