Selective protein-protein interactions driven by a phenylalanine interface

J Am Chem Soc. 2006 Jan 11;128(1):188-91. doi: 10.1021/ja055494k.

Abstract

Highly specific protein-protein interfaces have been the subject of considerable study for their potential utility in disrupting or interrogating cellular signaling and control networks. We report that coiled-coil sequences decorated with phenylalanine core residues fold into stable alpha-helical bundles and that these self-sort from similar peptide assemblies with aliphatic core side chains. For self-assembled ensembles derived from 30-residue monomeric peptides, the DeltaG of specificity is -1.5 kcal/mol, comparable with earlier self-sorting coiled-coil systems. Intriguingly, although this interface is constructed from canonical amino acids, it does not appear to have been exploited in native proteins.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Circular Dichroism
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / metabolism
  • Phenylalanine / chemistry*
  • Phenylalanine / metabolism
  • Protein Conformation
  • Substrate Specificity
  • Thermodynamics

Substances

  • Peptides
  • Phenylalanine