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Structure and hydration of membranes embedded with voltage-sensing domains

机译:嵌入电压感应域的膜的结构和水化

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摘要

Despite the growing number of atomic-resolution membrane protein structures, direct structural information about proteins in their native membrane environment is scarce. This problem is particularly relevant in the case of the highly charged S1-S4 voltage-sensing domains responsible for nerve impulses, where interactions with the lipid bilayer are critical for the function of voltage-activated ion channels. Here we use neutron diffraction, solid-state nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations to investigate the structure and hydration of bilayer membranes containing S1-S4 voltage-sensing domains. Our results show that voltage sensors adopt transmembrane orientations and cause a modest reshaping of the surrounding lipid bilayer, and that water molecules intimately interact with the protein within the membrane. These structural findings indicate that voltage sensors have evolved to interact with the lipid membrane while keeping energetic and structural perturbations to a minimum, and that water penetrates the membrane, to hydrate charged residues and shape the transmembrane electric field.%很多膜蛋白的X-射线晶体结构已被确定,但关rn于处在它们原始膜环境中的蛋白的直接结构信rn息却很少。现在,一项将中子衍射、固体NMRrn光谱和分子动态模拟结合起来的研究,为包含rnS1-S4电压感应域(它们被膜蛋白用来感应膜rn电压变化并对其做出反应)的类脂双层膜的结rn构和水合提供了一幅详细的画面。可以看到,rn这些电压传感器采用跨膜取向,使周围的类脂rn双层发生小幅度变形,但变形幅度之大足以让rn水分子能够与膜发生相互作用,从而使带电残rn体发生水合,使跨膜电场成形,同时将能量和rn结构扰动保持到最小程度。
机译:尽管原子分辨率的膜蛋白结构的数量不断增加,但有关其天然膜环境中蛋白的直接结构信息却很少。在负责神经冲动的高电荷S1-S4电压感应域的情况下,此问题尤其重要,其中与脂质双层的相互作用对于电压激活离子通道的功能至关重要。在这里,我们使用中子衍射,固态核磁共振(NMR)光谱和分子动力学模拟来研究包含S1-S4电压感测域的双层膜的结构和水合作用。我们的结果表明,电压传感器采用跨膜取向,并引起周围脂质双层的适度重塑,并且水分子与膜内的蛋白质紧密相互作用。这些结构上的发现表明,电压传感器已经发展为与脂质膜相互作用,同时将能量和结构扰动保持在最低限度,并且水渗透膜,水合带电的残留物并形成跨膜电场。射线晶体结构已被确定,但关rn于处在其原始膜环境中的蛋白的直接结构信rn息却很少。现在,一项将中子衍射,固体NMRrn光谱和分子动态模拟结合起来的研究,为包含rnS1-S4电压感应域(它们被膜蛋白转化为感应膜rn电压变化并引起反应)的类脂双层膜的结rn构和水合提供了一幅详细的画面。可以看到,rn这些电压传感器采用跨膜取向,使周围的类脂rn双层发生小幅度变形,但变形幅度之大允许rn水分子能够与膜发生相互作用,从而使带电残rn体发生水合,使跨膜突起成形,同时将能量和rn结构扰动保持到最小程度。

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  • 来源
    《Nature》 |2009年第7272期|473-479|共7页
  • 作者单位

    Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA;

    Department of Physiology and Biophysics, and Center for Biomembrane Systems, University of California, Irvine, California 92697, USA NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA;

    Department of Physiology and Biophysics, and Center for Biomembrane Systems, University of California, Irvine, California 92697, USA Department of Chemistry and Institute for Surface and Interface Science, University of California, Irvine, California 92697, USA;

    Department of Physics and Astronomy and Institute for Genomics and Bioinformatics, University of California, Irvine, California 92697, USA;

    Department of Physiology and Biophysics, and Center for Biomembrane Systems, University of California, Irvine, California 92697, USA NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA Biology Division, University of Missouri, Columbia, Missouri 65211, USA;

    Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda. Maryland 20892, USA;

    Department of Chemistry and Institute for Surface and Interface Science, University of California, Irvine, California 92697, USA;

    Department of Physiology and Biophysics, and Center for Biomembrane Systems, University of California, Irvine, California 92697, USA NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA;

    Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA;

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