文章基本信息

标题：Structure-based prediction of the stability of transmembrane helix–helix interactions: The sequence dependence of glycophorin A dimerization
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作者：Kevin R. MacKenzie ; Donald M. Engelman
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：7
页码：3583-3590
DOI：10.1073/pnas.95.7.3583
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The ability to predict the effects of point mutations on the interaction of -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.