Analysis of side-chain rotamers in transmembrane proteins
Analysis of side-chain rotamers in transmembrane proteins
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DOI：
10.1529/biophysj.104.044024
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发表时间：
2004-11-01
影响因子：
3.4
通讯作者：
Bowie, JU
中科院分区：
文献类型：
--
作者：
Chamberlain, AK;Bowie, JU
我们测量了14个α-螺旋和16个β-桶状膜蛋白结构中的侧链旋转异构体的频率，发现与可溶性蛋白质相比，膜环境对旋转异构体的频率有很大的扰动。尽管实验数据有限，但我们发现，根据残留物环境的不同，旋转异构体的偏好会发生统计上的显著变化。旋转异构体的分布受到残基是面向脂的还是面向蛋白质的，以及残基是否在N-端或C-端附近的影响。与螺旋骨架的氢键相互作用扰乱了Ser和His的旋转异构体数量。Trp和Tyr偏爱侧链构象，这种构象允许它们的侧链将它们的极性原子延伸到膜核心之外，从而使侧链的极性梯度与膜的极性梯度对齐。我们的结果展示了膜环境如何影响蛋白质的结构，为跨膜蛋白质的结构预测和设计提供了有用的信息。
We measured the frequency of side-chain rotamers in 14 alpha-helical and 16 beta-barrel membrane protein structures and found that the membrane environment considerably perturbs the rotamer frequencies compared to soluble proteins. Although there are limited experimental data, we found statistically significant changes in rotamer preferences depending on the residue environment. Rotamer distributions were influenced by whether the residues were lipid or protein facing, and whether the residues were found near the N- or C-terminus. Hydrogen-bonding interactions with the helical backbone perturbs the rotamer populations of Ser and His. Trp and Tyr favor side-chain conformations that allow their side chains to extend their polar atoms out of the membrane core, thereby aligning the side-chain polarity gradient with the polarity gradient of the membrane. Our results demonstrate how the membrane environment influences protein structures, providing information that will be useful in the structure prediction and design of transmembrane proteins.