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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca~(2+)·calmodulins
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Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca~(2+)·calmodulins

机译：Ca〜（2+）·钙调蛋白桥接的二聚体心脏L型钙通道调节域的晶体结构

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摘要

Voltage-dependent calcium channels (Ca_v) open in response to changes in membrane potential, but their activity is modulated by Ca~(2+) binding to calmodulin (CaM). Structural studies of this family of channels have focused on CaM bound to the IQ motif; however, the minimal differences between structures cannot adequately describe CaM's role in the regulation of these channels. We report a unique crystal structure of a 77-residue fragment of the Cav1.2 α_1 subunit carboxyl terminus, which includes a tandem of the pre-IQ and IQ domains, in complex with Ca~(2+)·CaM in 2 distinct binding modes. The structure of the Cav1.2 fragment is an unusual dimer of 2 coiled-coiled pre-IQ regions bridged by 2 Ca~(2+)·CaMs interacting with the pre-IQ regions and a canonical Ca_v1-IQ-Ca~(2+)·CaM complex. Native Ca_v 1.2 channels are shown to be a mixture of monomers/dimers and a point mutation in the pre-IQ region predicted to abolish the coiled-coil structure significantly reduces Ca~(2+)-dependent inactivation of heterologously expressed Ca_v1.2 channels.
机译：电压依赖性钙通道（Ca_v）响应膜电位的变化而打开，但其活性受Ca〜（2+）与钙调蛋白（CaM）结合的调节。该通道家族的结构研究集中于与智商基序结合的CaM。但是，结构之间的最小差异无法充分描述CaM在调节这些通道中的作用。我们报告了一个独特的晶体结构的Cav1.2α_1亚基羧基末端的77个残基片段，其中包括前IQ和IQ域的串联，与Ca〜（2+）·CaM结合成两个不同的结合模式。 Cav1.2片段的结构是2个卷曲螺旋预IQ区域的不寻常的二聚体，该区域由2个Ca〜（2+）·CaM桥接，与预IQ区域相互作用，并且典范Ca_v1-IQ-Ca〜（2 +）·CaM复合体。天然的Ca_v 1.2通道显示为单体/二聚体的混合物，并且预IQ区中的点突变预计将消除卷曲螺旋结构，从而显着减少异源表达的Ca_v1.2通道的Ca〜（2+）依赖性失活。

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  • 作者

    Jennifer L. Fallon; Mariah R. Baker; Liangwen Xiong; Ryan E. Loy; Guojun Yang; Robert T. Dirksen; Susan L. Hamilton; Florante A. Quiocho;

  • 作者单位

    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030;

    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030 Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030;

    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030;

    Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642;

    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030;

    Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642;

    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030 Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030;

    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030 Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    structure; function; voltage-gated calcium channel;

    机译：结构体;功能;电压门控钙通道;

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