A study on the effect of synthetic α-to-β3-amino acid mutations on the binding of phosphopeptides to 14-3-3 proteins

Chem Commun (Camb). 2019 Dec 5;55(98):14809-14812. doi: 10.1039/c9cc07982c.

Abstract

Here we describe the synthesis of a series of α,β-phosphopeptides, based on the phosphoepitope site on YAP1 (yes-associated protein 1), and the biochemical, biophysical and structural characterization of their binding to 14-3-3 proteins. The impact of systematic mono- and di-substitution of α → β3 amino acid residues around the phosphoserine residue are discussed. Our results confirm the important role played by the +2 proline residue in the thermodynamics and structure of the phosphoepitope/14-3-3 interaction.

MeSH terms

  • 14-3-3 Proteins / chemistry
  • 14-3-3 Proteins / metabolism*
  • Adaptor Proteins, Signal Transducing / chemistry
  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Amino Acids / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Phosphopeptides / chemical synthesis
  • Phosphopeptides / chemistry
  • Phosphopeptides / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • Thermodynamics
  • Transcription Factors / chemistry
  • YAP-Signaling Proteins

Substances

  • 14-3-3 Proteins
  • Adaptor Proteins, Signal Transducing
  • Amino Acids
  • Phosphopeptides
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human