Fairman R, Shoemaker K R, York E J, Stewart J M, Baldwin R L
Department of Biochemistry, Stanford University Medical Center, California 94305.
Proteins. 1989;5(1):1-7. doi: 10.1002/prot.340050102.
Interactions between the alpha-helix peptide dipoles and charged groups close to the ends of the helix were found to be an important determinant of alpha-helix stability in a previous study. The charge on the N-terminal residue of the C-peptide from ribonuclease A was varied chiefly by changing the alpha-NH2 blocking group, and the correlation of helix stability with N-terminal charge was demonstrated. An alternative explanation for some of those results is that the succinyl and acetyl blocking groups stabilize the helix by hydrogen bonding to an unsatisfied main-chain NH group. The helix dipole model is tested here with peptides that contain either a free alpha-NH3+ or alpha-COO- group, and no other charged groups that would titrate with similar pKa's. This model predicts that alpha-NH3+ and alpha-COO- groups are helix-destabilizing and that the destabilizing interactions are electrostatic in origin. The hydrogen bonding model predicts that alpha-NH3+ and alpha-COO- groups are not themselves helix-destabilizing, but that an acetyl or amide blocking group at the N- or C-terminus, respectively, stabilizes the helix by hydrogen bonding to an unsatisfied main-chain NH or CO group. The results are as follows: (1) Removal of the charge from alpha-NH3+ and alpha-COO- groups by pH titration stabilizes an alpha-helix. (2) The increase in helix stability on pH titration of these groups is close to the increase produced by adding an acetyl or amide blocking group.(ABSTRACT TRUNCATED AT 250 WORDS)
