兰尼碱受体1结构及其通道门控机制的研究进展
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第二军医大学临床医学专业学员十一队,第二军医大学海军临床医学专业学员三队,第二军医大学海军医学系,第二军医大学海军医学系海洋生物技术教研室

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国家自然科学基金面上项目(81470518),2015年度第二军医大学大学生创新基金面上项目(MS2015014,MS2015028).


Ryanodine receptor 1 and its potential gating mechanism: recent progress
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Grade 2013,Clinical Medicine,Second Military Medical University,Shanghai,Grade 2013,Naval Clinical Medicine,Faculty of Naval Medicine,Second Military Medical University,Shanghai,Faculty of Naval Medicine,Second Military Medical University,Shanghai,Department of Marine Biotechnology,Faculty of Naval Medicine,Second Military Medical University,Shanghai

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Supported by National Natural Science Foundation of China (81470518) and Innovation Fund for Students of Second Military Medical University of 2015 (MS2015014, MS2015028).

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    摘要:

    兰尼碱受体(ryanodine receptor, RyR)是位于肌浆网膜上的细胞内Ca2+释放通道,在骨骼肌和心肌兴奋收缩偶联等生理过程中发挥重要作用。随着单粒子冷冻电镜技术的应用以及数据分析能力的提高,近期来自中国、美国以及德国的3个课题组分别获得了整体分辨率为3.8Å (1Å=10-10m)、4.8Å和6.1Å的高清晰RyR1结构图片,相关研究同时发表于2015年第1期的Nature上,是近年来RyR结构及其门控研究的重要进展。RyR1为相对分子质量>2200000的同源四聚体离子通道,主要包括由NTD、SPRY、P1、P2、B-sol以及C-sol等结构域组成的胞质区和由S1~S6、VSL以及CTD等结构域组成的通道区。Ca2+作为RyR1门控的主要影响因子,能够与胞质区EF-hand亚结构域结合,引起通道构象的变化并最终导致通道的开放。

    Abstract:

    The ryanodine receptors (RyRs) are intracellular Ca2+ releasing channels on the sarcoplasmic reticulum membrane and play a pivotal role in the excitation-contraction coupling of skeletal and cardiac muscles as well as other physiological processes. With the recent development of Cryo-EM and the improvement of data analysis technique, scientists from China, the United States and Germany have acquired high-quality RyR1 images at the total resolutions of 3.8 Å (1 Å=10-10 m), 4.8 Å and 6.1 Å, respectively, which have been published in the same issue of Nature in 2015. RyR1s are homotetrameric complexes with a molecular mass of more than 2200000, mainly containing a cytoplasmic region composed of NTD, SPRY, P1, P2, B-sol and C-sol domains and a channel region composed of S1-S6, VSL and CTD domains. As the most common factor affecting the condition of RyR1, Ca2+ is able to bind the EF-hand subdomain in the cytoplasmic region, which further causes the conformational change and finally leads to the channel opening.

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  • 收稿日期:2016-03-15
  • 最后修改日期:2016-06-07
  • 录用日期:2016-07-07
  • 在线发布日期: 2016-07-27
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