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Modest stabilization by most hydrogen-bonded side-chain interactions in membrane proteins

机译：膜蛋白中大多数氢键侧链相互作用的适度稳定作用

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摘要

Understanding the energetics of molecular interactions is fundamental to all of the central quests of structural biology including structure prediction and design, mapping evolutionary pathways, learning how mutations cause disease, drug design, and relating structure to function. Hydrogen-bonding is widely regarded as an important force in a membrane environment because of the low dielectric constant of membranes and a lack of competition from water. Indeed, polar residue substitutions are the most common disease-causing mutations in membrane proteins. Because of limited structural information and technical challenges, however, there have been few quantitative tests of hydrogen-bond strength in the context of large membrane proteins. Here we show, by using a double-mutant cycle analysis, that the average contribution of eight interhelical side-chain hydrogen-bonding interactions throughout bacteriorhodopsin is only 0.6 kcalmol~(-1). In agreement with these experiments, we find that 4% of polar atoms in the non-polar core regions of membrane proteins have no hydrogen-bond partner and the lengths of buried hydrogen bonds in soluble proteins and membrane protein transmembrane regions are statistically identical. Our results indicate that most hydrogen-bond interactions in membrane proteins are only modestly stabilizing. Weak hydrogen-bonding should be reflected in considerations of membrane protein folding, dynamics, design, evolution and function.
机译：了解分子相互作用的能量学是结构生物学所有核心任务的基础，包括结构预测和设计，绘制进化途径，了解突变如何导致疾病，药物设计以及将结构与功能联系起来。由于膜的介电常数低且缺乏与水的竞争性，氢键被广泛认为是膜环境中的重要力量。实际上，极性残基取代是膜蛋白中最常见的致病突变。由于有限的结构信息和技术挑战，然而，在大膜蛋白的情况下，很少有氢键强度的定量测试。在这里，我们通过双突变周期分析表明，整个细菌视紫红质中八个螺旋间侧链氢键相互作用的平均贡献仅为0.6 kcalmol〜（-1）。与这些实验相一致，我们发现膜蛋白的非极性核心区域中的4％极性原子没有氢键伴侣，可溶性蛋白和膜蛋白跨膜区域中掩埋氢键的长度在统计上是相同的。我们的结果表明，膜蛋白中的大多数氢键相互作用仅适度稳定。弱氢键应反映在膜蛋白折叠，动力学，设计，进化和功能方面。

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  • 来源
    《Nature》 |2008年第7198期|1266-1270|共5页
  • 作者

    Nathan HyunJoong Joh; Andrew Min; Salem Faham; Julian P. Whitelegge; Duan Yang; Virgil L. Woods Jr; James U. Bowie;

  • 作者单位

    Department of Chemistry and Biochemistry, UCLA-DOE Center for Genomics and Proteomics, Molecular Biology Institute;

    Department of Chemistry and Biochemistry, UCLA-DOE Center for Genomics and Proteomics, Molecular Biology Institute;

    Department of Physiology, and Pasarow Mass Spec Laboratory, University of California, Los Angeles, California 90095, USA;

    The NPI-Semel Institute, Pasarow Mass Spec Laboratory, University of California, Los Angeles, California 90095, USA;

    Department of Chemistry and Biochemistry, UCLA-DOE Center for Genomics and Proteomics, Molecular Biology Institute;

    Department of Medicine and Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, California 92093-0656, USA;

    Department of Chemistry and Biochemistry, UCLA-DOE Center for Genomics and Proteomics, Molecular Biology Institute;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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