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Pore architecture and ion sites in acid-sensing ion channels and P2X receptors

机译：酸敏感离子通道和P2X受体中的孔结构和离子位点

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摘要

Acid-sensing ion channels are proton-activated, sodium-selective channels composed of three subunits, and are members of the superfamily of epithelial sodium channels, mechanosensitive and FMRF-amide peptide-gated ion channels. These ubiquitous eukaryotic ion channels have essential roles in biological activities as diverse as sodium homeostasis, taste and pain. Despite their crucial roles in biology and their unusual trimeric subunit stoichiometry, there is little knowledge of the structural and chemical principles underlying their ion channel architecture and ion-binding sites. Here we present the structure of a functional acid-sensing ion channel in a desensitized state at 3 A resolution, the location and composition of the～rn8A 'thick' desensitization gate, and the trigonal antiprism coordination of caesium ions bound in the extracellular vestibule. Comparison of the acid-sensing ion channel structure with the ATP-gated P2X_4 receptor reveals similarity in pore architecture and aqueous vestibules, suggesting that there are unanticipated yet common structural and mechanistic principles.
机译：酸敏感离子通道是质子活化的钠选择性通道，由三个亚基组成，并且是上皮钠通道，机械敏感和FMRF-酰胺肽门控离子通道超家族的成员。这些普遍存在的真核生物离子通道在生物活动中起着至关重要的作用，例如钠稳态，味道和疼痛。尽管它们在生物学中起着至关重要的作用，而且它们的三聚体亚基化学计量也不同寻常，但对其离子通道结构和离子结合位点背后的结构和化学原理了解甚少。在这里，我们介绍了在3 A分辨率下处于脱敏状态的功能性酸敏感离子通道的结构，〜rn8A“厚”脱敏门的位置和组成，以及结合在细胞外前庭中的铯离子的三角反棱镜配位。酸感应离子通道结构与ATP门控的P2X_4受体的比较揭示了孔结构和水性前庭的相似性，这表明存在意料之外但常见的结构和机理原理。

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  • 来源
    《Nature》 |2009年第7255期|599-604|共6页
  • 作者

    Eric B. Gonzales; Toshimitsu Kawate; Eric Gouaux;

  • 作者单位

    Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA;

    Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA;

    Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA Howard Hughes Medical Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, 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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  • 正文语种 eng
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