Side-chain interactions in the C-peptide helix: Phe 8 ... His 12+

Biopolymers. 1990 Jan;29(1):1-11. doi: 10.1002/bip.360290104.


Previous studies have demonstrated that His 12 plays a major role in the pH-dependent stability of the helix formed by the isolated C-peptide (residues 1-13 of ribonuclease A). Here, amino acid replacement experiments show that His 12+ stabilizes the C-peptide helix chiefly by interacting with Phe 8. The Phe 8 ... His 12+ ring interaction is specific for the protonated form of His 12 (His 12+) and the interaction is not screened significantly by NaCl, unlike the charged group ... helix dipole interactions studied earlier in C-peptide. Analogs of C-peptide that are unable to form the Phe 8 ... His 12+ interaction show large increases in helix content for Phe----Ala and His----Ala. Therefore, the helical tendencies of the individual residues Phe, His, and Ala are important in determining the result of a replacement experiment. Since the side chains of Phe 8 and His 12 probably interact within the N-terminal helix of ribonuclease A, the existence of the Phe 8 ... His 12+ interaction in the isolated C-peptide helix adds to the evidence that the C-peptide helix is an autonomous folding unit.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Histidine*
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Peptide Fragments*
  • Phenylalanine*
  • Protein Conformation
  • Ribonuclease, Pancreatic*
  • Sodium Chloride


  • Peptide Fragments
  • Sodium Chloride
  • Phenylalanine
  • Histidine
  • Ribonuclease, Pancreatic