Effect of alanine versus glycine in α-helices on protein stability
- 1 April 1992
- journal article
- research article
- Published by Springer Nature in Nature
- Vol. 356 (6368), 453-455
- https://doi.org/10.1038/356453a0
Abstract
THE rational design of proteins requires knowledge of the helix-forming propensities (s-values) of the different amino acids. There is, however, considerable controversy about the relative values for alanine and glycine1–12We find from experiments on mutants of barnase that the relative effect of Ala versus Gly on helix stability depends crucially on the position in the helix (whether they are at the ends (caps) or are internal) and the context (the influence of their neighbours). Glycine is greatly preferred at the N and C caps. At internal positions, Ala stabilizes the helix relative to Gly by 0.4 to 2 kcal mol−1. The variation results from a combination of burial of hydrophobic surface on folding and interference with hydrogen bonding of the protein with solvent. There is a good empirical correlation between the relative stabilizing effects of Ala and Gly with the total change in solvent-accessible hydrophobic surface area of the folded protein on mutation of Gly to Ala. It is not valid to assign to each amino acid a unique s-value that is generally applicable to all positions in all helices in all proteins.Keywords
This publication has 30 references indexed in Scilit:
- Alarums and diversionsNature, 1991
- COSMIC analysis of the major α-helix of barnase during foldingJournal of Molecular Biology, 1991
- Aromatic-aromatic interactions and protein stabilityJournal of Molecular Biology, 1991
- Strength and co-operativity of contributions of surface salt bridges to protein stabilityJournal of Molecular Biology, 1990
- A Thermodynamic Scale for the Helix-Forming Tendencies of the Commonly Occurring Amino AcidsScience, 1990
- Effect of the substitution Ala .fwdarw. Gly at each of five residue positions in the C-peptide helixBiochemistry, 1989
- GAL4-VP16 is an unusually potent transcriptional activatorNature, 1988
- Interior and surface of monomeric proteinsJournal of Molecular Biology, 1987
- Helix-coil stability constants for the naturally occurring amino acids in water. 22. Histidine parameters from random poly[(hydroxybutyl)glutamine-co-L-histidine]Macromolecules, 1984
- Environment and exposure to solvent of protein atoms. Lysozyme and insulinJournal of Molecular Biology, 1973