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Structural mechanism of C-type inactivation in K~+ channels

机译：K〜+通道C型失活的结构机理

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摘要

Interconversion between conductive and non-conductive forms of the K~+ channel selectivity filter underlies a variety of gating events, from flicker transitions (at the microsecond timescale) to C-type inactivation (millisecond to second timescale). Here we report the crystal structure of the Streptomyces lividans K~+ channel KcsA in its open-inactivated conformation and investigate the mechanism of C-type inactivation gating at the selectivity filter from channels 'trapped' in a series of partially open conformations. Five conformer classes were identified with openings ranging from 12 A in closed KcsA (Cα-Cα distances at Thr 112) to 32 A when fully open. They revealed a remarkable correlation between the degree of gate opening and the conformation and ion occupancy of the selectivity filter. We show that a gradual filter backbone reorientation leads first to a loss of the S2 ion binding site and a subsequent loss of the S3 binding site, presumably abrogating ion conduction. These structures indicate a molecular basis for C-type inactivation in K~+ channels.
机译：K〜+通道选择性滤波器的导电形式和非导电形式之间的相互转换是各种门控事件的基础，从闪烁过渡（以微秒为时标）到C型失活（毫秒至以秒为时标）。在这里，我们报告了链霉菌链霉菌K〜+通道KcsA处于开放灭活构象的晶体结构，并研究了C型失活门控在选择性过滤器上从一系列部分开放构象中“困住”的通道的机制。确定了五种一致性等级，其开口范围从闭合KcsA中的12 A（Thr 112处的Cα-Cα距离）到完全打开时的32A。他们揭示了选通滤波器的开度与构象和离子占有率之间的显着相关性。我们表明，逐渐的过滤器主链重新定向首先导致S2离子结合位点的损失和随后的S3结合位点的损失，大概是消除了离子传导。这些结构表明了K +通道中C型失活的分子基础。

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  • 来源
    《Nature》 |2010年第7303期|P.203-208|共6页
  • 作者

    Luis G. Cuello; rnVishwanath Jogini; rnD. Marien Cortes; rnEduardo Perozo;

  • 作者单位

    Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA Department of Cell Physiology and Molecular Biophysics, Texas Tech University, Lubbock, Texas 79430, USA;

    rnDepartment of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA Department of Cell Physiology and Molecular Biophysics, Texas Tech University, Lubbock, Texas 79430, USA D. E. Shaw Research, Hyderabad 500034, India;

    rnDepartment of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA Department of Cell Physiology and Molecular Biophysics, Texas Tech University, Lubbock, Texas 79430, USA;

    rnDepartment of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA;

  • 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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