NIH首席研究员《Nature》揭开原始膜蛋白神秘面纱

　　

生物通报道，NIH旗下神经失调症与中风研究所（National Institute of Neurological Disorders and Stroke），加州大学生物膜系统研究中心，密苏里大学生物系等处的研究者在最近的一期Nature杂志上发表了膜蛋白研究的最新进展文章Structure and hydration of membranes embedded with voltage-sensing domains。

 

文章通讯作者，该研究的领导者是来自NIH旗下神经失调症与中风研究所（NINDS）的资深研究员Kenton J. Swartz教授，他于1986年毕业于Eastern Mennonite学院生物化学系，1992年获得哈佛大学神经生物学博士学位，追随Bruce Bean学习钙离子依赖性的压力门通路研究，其后在哈佛大学从事博士后研究，并首次分离到影响钙离子通道的毒素，1997年加入NINDS，2003年升为资深研究员。目前拥有自己的实验室，主要学从事电压离子通道的分子机制的研究工作。

 

膜蛋白是指能够结合或整合到细胞或细胞器的膜上的蛋白质的总称。而细胞中一半以上的蛋白质可以与膜以不同形式结合。根据与膜结合强度的不同，膜蛋白可以被分为两类：外周膜蛋白和内在膜蛋白。

 

随着蛋白结构生物学的发展，很多膜蛋白的X-射线晶体结构已被确定，但关于处在它们原始膜环境中的蛋白的直接结构信息却很少。

 

现在，Swartz博士带领的研究小组将中子衍射、固体NMR光谱和分子动态模拟结合起来研究原始环境中的膜蛋白结构，为包含S1-S4电压感应域（它们被膜蛋白用来感应膜电压变化并对其做出反应）的类脂双层膜的结构和水合提供了一幅详细的画面。

 

研究结果表明，这些电压传感器采用跨膜取向，使周围的类脂双层发生小幅度变形，但变形幅度之大足以让水分子能够与膜发生相互作用，从而使带电残体发生水合，使跨膜电场成形，同时将能量和结构扰动保持到最小程度。

（生物通 小茜）

生物通推荐原文检索

Structure and hydration of membranes embedded with voltage-sensing domains

Dmitriy Krepkiy1,8, Mihaela Mihailescu2,5,8, J. Alfredo Freites2,3, Eric V. Schow4, David L. Worcester2,5,6, Klaus Gawrisch7, Douglas J. Tobias3, Stephen H. White2,5 & Kenton J. Swartz1

 

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,

Department of Chemistry and Institute for Surface and Interface Science,

Department of Physics and Astronomy and Institute for Genomics and Bioinformatics, 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

These authors contributed equally to this work.

Correspondence to: Stephen H. White2,5Kenton J. Swartz1 Correspondence and requests for materials should be addressed to S.H.W. (Email: [e-mail]) or K.J.S. (Email: [e-mail]).

 

 

【Abstract】

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.