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Updated: Aug 5, 2026

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
Structure-based prediction of the stability of transmembrane helix-helix interactions: the sequence dependence of
1Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Ave., New Haven, CT 06520, USA.
Abstract:
The ability to predict the effects of point mutations on the interaction of alpha-helices within membranes would represent a significant step toward understanding the folding and stability of membrane proteins. We use structure-based empirical parameters representing steric clashes, favorable van der Waals interactions, and restrictions of side-chain rotamer freedom to explain the relative dimerization propensities of 105 hydrophobic single-point mutants of the glycophorin A (GpA) transmembrane domain. Although the structure at the dimer interface is critical to our model, changes in side-chain hydrophobicity are uncorrelated with dimer stability, indicating that the hydrophobic effect does not influence transmembrane helix-helix association. Our model provides insights into the compensatory effects of multiple mutations and shows that helix-helix interactions dominate the formation of specific structures.
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