Transient domain interactions enhance the affinity of the mitotic regulator Pin1 toward phosphorylated peptide ligands

Anja Matena, Christian Sinnen, Johannes van den Boom, Christoph Wilms, J Nikolaj Dybowski, Ricarda Maltaner, Jonathan W Mueller, Nina M Link, Daniel Hoffmann, Peter Bayer

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


The mitotic regulator Pin1 plays an important role in protein quality control and age-related medical conditions such as Alzheimer disease and Parkinson disease. Although its cellular role has been thoroughly investigated during the past decade, the molecular mechanisms underlying its function remain elusive. We provide evidence for interactions between the two domains of Pin1. Several residues displayed unequivocal peak splits in nuclear magnetic resonance spectra, indicative of two different conformational states in equilibrium. Pareto analysis of paramagnetic relaxation enhancement data demonstrates that the two domains approach each other upon addition of a nonpeptidic ligand. Titration experiments with phosphorylated peptides monitored by fluorescence anisotropy and chemical shift perturbation indicate that domain interactions increase Pin1's affinity toward peptide ligands. We propose this interplay of the domains and ligands to be a general mechanism for a large class of two-domain proteins.

Original languageEnglish
Pages (from-to)1769-1777
Number of pages9
Issue number10
Publication statusPublished - 8 Oct 2013


  • Fluorescence Polarization
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptidylprolyl Isomerase
  • Phosphopeptides
  • Polyethylene Glycols
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • Solutions
  • Solvents
  • Thermodynamics


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