MacKenzie K R, Engelman D M
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Ave., New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3583-90. doi: 10.1073/pnas.95.7.3583.
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.
预测点突变对膜内α螺旋相互作用的影响，将是朝着理解膜蛋白折叠和稳定性迈出的重要一步。我们使用基于结构的经验参数来表示空间冲突、有利的范德华相互作用以及侧链旋转异构体自由度的限制，以解释血型糖蛋白A（GpA）跨膜结构域105个疏水单点突变体的相对二聚化倾向。尽管二聚体界面处的结构对我们的模型至关重要，但侧链疏水性的变化与二聚体稳定性无关，这表明疏水效应不会影响跨膜螺旋-螺旋缔合。我们的模型为多个突变的补偿效应提供了见解，并表明螺旋-螺旋相互作用主导了特定结构的形成。
