Structure of IP(3)R channel: high-resolution insights from cryo-EM.

Structure of IP(3)R channel: high-resolution insights from cryo-EM.
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DOI:
10.1016/j.sbi.2017.05.014
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发表时间:
2017-10
影响因子:
6.8
通讯作者:
Serysheva II
Serysheva II
中科院分区:
生物学2区
文献类型:
--
作者:
Baker MR;Fan G;Serysheva II

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肌醇1,4,5-三磷酸受体(IP3Rs)是广泛表达的细胞内钙离子通道,是细胞内钙离子对各种细胞外刺激的反应所产生的钙信号的主要介体。尽管IP3R通道在许多人类疾病中的生理意义已经确立,并且已被证实参与其中,但这些离子通道及其门控信号检测的详细结构基础仍然不清楚。最近,单粒子电子冷冻显微镜(CRYO-EM)已经获得了期待已久的全长1型IP3R的近原子分辨结构。这种结构为IP3R的分子组装提供了令人兴奋的机制见解,揭示了钙释放通道明显的结构保守性,并提出了许多关于其激活和门控的基本和有争议的问题。在这里,我们总结了推动我们的IP3R低温EM分析达到近原子分辨率的主要技术进步,并讨论了钙释放通道的结构生物学的未来。
Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ubiquitously expressed intracellular Ca2+ channels and the major mediators of cellular Ca2+ signals generated by the release of Ca2+ ions from intracellular stores in response to a variety of extracellular stimuli. Despite established physiological significance and proven involvements of IP3R channels in many human diseases, detailed structural basis for signal detection by these ion channels and their gating remain obscure. Recently, single particle electron cryomicroscopy (cryo-EM) has yielded a long-awaited near-atomic resolution structure of the entire full-length type 1 IP3R. This structure provided exciting mechanistic insights into the molecular assembly of IP3R, revealing the pronounced structural conservation of Ca2+ release channels and raising many fundamental and controversial questions on their activation and gating. Here we summarize the major technological advances that propelled our cryo-EM analysis of IP3R to near-atomic resolution and discuss what the future holds for structural biology of Ca2+ release channels.
DOI: 10.1038/nature15249
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