A Cα-H...O hydrogen bond in a membrane protein is not stabilizing

Hydrogen bonds involving a carbon donor are very common in protein structures, and energy calculations suggest that Calpha-H...O hydrogen bonds could be about one-half the strength of traditional hydrogen bonds. It has therefore been proposed that these nontraditional hydrogen bonds could be a signi...

Full description

Saved in:
Bibliographic Details
Published inJournal of the American Chemical Society Vol. 126; no. 8; pp. 2284 - 2285
Main Authors YOHANNAN, Sarah, FAHAM, Salem, DUAN YANG, GROSFELD, David, CHAMBERLAIN, Aaron K, BOWIE, James U
Format Journal Article
LanguageEnglish
Published Washington, DC American Chemical Society 03.03.2004
Subjects
Amino Acid Substitution
Bacteriorhodopsins - chemistry
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Hydrogen Bonding
Interactions. Associations
Intermolecular phenomena
Models, Molecular
Molecular biophysics
Mutagenesis, Site-Directed
Protein Folding
Protein Structure, Secondary
Thermodynamics
Bacteriorhodopsin
Membrane protein
Molecular structure
Molecular association
Molecular interaction
Thermodynamic stability
Hydrogen bond
Online AccessGet full text

Cover

More Information
Summary:Hydrogen bonds involving a carbon donor are very common in protein structures, and energy calculations suggest that Calpha-H...O hydrogen bonds could be about one-half the strength of traditional hydrogen bonds. It has therefore been proposed that these nontraditional hydrogen bonds could be a significant factor in stabilizing proteins, particularly membrane proteins as there is a low dielectric and no competition from water in the bilayer core. Nevertheless, this proposition has never been tested experimentally. Here, we report an experimental test of the significance of Calpha-H...O bonds for protein stability. Thr24 in bacteriorhodopsin, which makes an interhelical Calpha-H...O hydrogen bond to the Calpha of Ala51, was changed to Ala, Val, and Ser, and the thermodynamic stability of the mutants was measured. None of the mutants had significantly reduced stability. In fact, T24A was more stable than the wild-type protein by 0.6 kcal/mol. Crystal structures were determined for each of the mutants, and, while some structural changes were seen for T24S and T24V, T24A showed essentially no apparent structural alteration that could account for the increased stability. Thus, Thr24 appears to destabilize the protein rather than stabilize. Our results suggest that Calpha-H...O bonds are not a major contributor to protein stability.
ISSN:0002-7863
1520-5126