Side-chain interactions in the C-peptide helix: Phe 8 ... His 12+.
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.
Shoemaker
K R
KR
Department of Biochemistry, Stanford University, California 94305.
Fairman
R
R
Schultz
D A
DA
Robertson
A D
AD
York
E J
EJ
Stewart
J M
JM
Baldwin
R L
RL
D000595:Amino Acid Sequence; D006639:Histidine; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010649:Phenylalanine; D011487:Protein Conformation; D012259:Ribonuclease, Pancreatic; D012965:Sodium Chloride
D010446:Peptide Fragments; D012965:Sodium Chloride; D010649:Phenylalanine; D006639:Histidine; D012259:Ribonuclease, Pancreatic