nature

当前位置: Nature » 细胞生物学 » 正文

Nature:颜宁、施一公再发重量级成果

摘要 : 日前,清华大学和MRC分子生物学实验室的研究团队通过单颗粒低温电子显微技术,解析了兔RyR1与其调节子FKBP12结合时的结构,总体分辨率达到了3.8 Å。这一成果于12月15日发表在Nature杂志上网站上,文章的通讯作者是清华大学的颜宁教授、施一公院士和MRC分子生物学实验室的jors H. W. Scheres。

 颜宁、施一公Nature再发重量级成果

日前,清华大学和MRC分子生物学实验室的研究团队通过单颗粒低温电子显微技术,解析了兔RyR1与其调节子FKBP12结合时的结构,总体分辨率达到了3.8 Å。这一成果于12月15日发表在Nature杂志上网站上,文章的通讯作者是清华大学的颜宁教授、施一公院士和MRC分子生物学实验室的jors H. W. Scheres。

Ryanodine受体(RyR)是细胞内一种高度导电的钙离子通道,在肌肉的兴奋-收缩偶联中起到了关键性的作用。哺乳动物共有三种RyR(RyR1、RyR2和RyR3),这三种RyR共享70%的序列。其中RyR1和RyR2主要在骨骼肌和心肌表达,而RyR3是在大脑中发现的。

RyR是已知最大的离子通道,这个同源四聚体的每个原体(protomer)含有差不多五千个残基。RyR主要分为细胞质区域和跨膜区域,四个相同的跨膜片段围出了核心通道,而细胞质区域负责感知多种配体,包括离子和蛋白(钙离子是RyR的主要调节子)。在此基础上,RyR可以应答不同刺激的复杂调控。

研究人员鉴定了三个新结构域(central、handle和helical结构域),这些结构域和氨基末端结构域为配体结合和构象改变奠定了基础。研究显示,RyR1的通道区域表现出了电压门控离子通道超家族的明显特征。

文章指出,通道区域和细胞质区域的分辨率达到了近原子水平,足以从头建立原子模型。这项研究有助于人们进一步理解RyR的结构、功能及其通道活性的别构调节。

原文标题:Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution

原文摘要:The ryanodine receptors (RyRs) are high-conductance intracellular Ca2+ channels that play a pivotal role in the excitation–contraction coupling of skeletal and cardiac muscles. RyRs are the largest known ion channels, with a homotetrameric organization and approximately 5,000 residues in each protomer. Here we report the structure of the rabbit RyR1 in complex with its modulator FKBP12 at an overall resolution of 3.8 Å, determined by single-particle electron cryomicroscopy. Three previously uncharacterized domains, named central, handle and helical domains, display the armadillo repeat fold. These domains, together with the amino-terminal domain, constitute a network of superhelical scaffold for binding and propagation of conformational changes. The channel domain exhibits the voltage-gated ion channel superfamily fold with distinct features. A negative-charge-enriched hairpin loop connecting S5 and the pore helix is positioned above the entrance to the selectivity-filter vestibule. The four elongated S6 segments form a right-handed helical bundle that closes the pore at the cytoplasmic border of the membrane. Allosteric regulation of the pore by the cytoplasmic domains is mediated through extensive interactions between the central domains and the channel domain. These structural features explain high ion conductance by RyRs and the long-range allosteric regulation of channel activities.

来源: Nature 浏览次数:165

热门文章TOP

RSS订阅 - 填写您的邮件地址,订阅我们的精彩内容: - 网站地图
网站联系电话:020-87540820 备案号:粤ICP备11050685号-8 增值电信业务经营许可证:粤B2-20120479
©2011-2015 生物帮 All rights reserved.