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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Predicting weakly stable regions, oligomerization state, and protein-protein interfaces in transmembrane domains of outer membrane proteins
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Predicting weakly stable regions, oligomerization state, and protein-protein interfaces in transmembrane domains of outer membrane proteins

机译：预测外膜蛋白跨膜结构域中的弱稳定区域，低聚状态和蛋白-蛋白界面

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摘要

Although the structures of many β-barrel membrane proteins are available, our knowledge of the principles that govern their energetics and oligomerization states is incomplete. Here we describe a computational method to study the transmembrane (TM) domains of β-barrel membrane proteins. Our method is based on a physical interaction model, a simplified conformational space for efficient enumeration, and an empirical potential function from a detailed combinatorial analysis. Using this method, we can identify weakly stable regions in the TM domain, which are found to be important structural determinants for β-barrel membrane proteins. By calculating the melting temperatures of the TM strands, our method can also assess the stability of β-barrel membrane proteins. Predictions on membrane enzyme PagP are consistent with recent experimental NMR and mutant studies. We have also discovered that out-clamps, in-plugs, and oligomerization are 3 general mechanisms for stabilizing weakly stable TM regions. In addition, we have found that extended and contiguous weakly stable regions often signal the existence of an oligomer and that strands located in the interfaces of protein-protein interactions are considerably less stable. Based on these observations, we can predict oligomerization states and can identify the interfaces of protein-protein interactions for β-barrel membrane proteins by using either structure or sequence information. In a set of 25 nonhomologous proteins with known structures, our method successfully predicted whether a protein forms a monomer or an oligomer with 91% accuracy; in addition, our method identified with 82% accuracy the protein-protein interaction interfaces by using sequence information only when correct strands are given.
机译：尽管可以获得许多β-桶状膜蛋白的结构，但我们对控制其能量和低聚状态的原理的知识尚不完善。在这里，我们描述了一种计算方法来研究β-桶状膜蛋白的跨膜（TM）域。我们的方法基于一个物理交互模型，一个简化的构象空间（可进行有效枚举）以及通过详细的组合分析得出的经验势函数。使用这种方法，我们可以确定TM域中的弱稳定区域，这些区域被发现是β-桶状膜蛋白的重要结构决定因素。通过计算TM链的解链温度，我们的方法还可以评估β-桶状膜蛋白的稳定性。膜酶PagP的预测与最近的实验NMR和突变体研究一致。我们还发现，钳外，塞内和低聚是稳定弱稳定TM区的3种通用机理。另外，我们已经发现，延伸的和连续的弱稳定区域经常表示寡聚体的存在，并且位于蛋白质与蛋白质相互作用的界面中的链的稳定性大大降低。基于这些观察结果，我们可以预测寡聚化状态，并可以通过使用结构或序列信息来确定β-桶形膜蛋白的蛋白质-蛋白质相互作用的界面。在一组25种结构已知的非同源蛋白质中，我们的方法成功地预测了蛋白质形成单体还是寡聚体的准确度为91％。此外，我们的方法仅在给出正确链的情况下，才使用序列信息以82％的精度识别蛋白质-蛋白质相互作用界面。

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