Crystal structure of the natural anion-conducting channelrhodopsin GtACR1.

Crystal structure of the natural anion-conducting channelrhodopsin GtACR1.
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DOI:
10.1038/s41586-018-0511-6
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发表时间:
2018-09
期刊:
影响因子:
64.8
通讯作者:
Deisseroth K
Deisseroth K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kim YS;Kato HE;Yamashita K;Ito S;Inoue K;Ramakrishnan C;Fenno LE;Evans KE;Paggi JM;Dror RO;Kandori H;Kobilka BK;Deisseroth K

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在隐生藻类 Guillardia theta 中发现的天然存在的通道视紫红质变体阴离子通道视紫红质-1 (ACR1),在异源环境中表达时表现出大的光门控阴离子电导和高阴离子选择性,这些特性支持其用作抑制神经元光放电的光遗传学工具。然而,由于缺乏光门控阴离子电导基础的结构信息,因此缺乏对 ACR1 的分子洞察。在这里,我们以 2.9 Å 分辨率展示了 G. theta ACR1 的晶体结构。该结构揭示了跨越细胞外结构域、视网膜结合袋、席夫碱区和阴离子传导通路的不寻常的结构特征。结合电生理学和光谱分析,这些发现揭示了自然发生的光门控阴离子电导的基本分子基础,并为设计下一代光遗传学工具提供了框架。来自海藻 Guillardia theta 的阴离子通道视紫红质-1 (ACR1) 的晶体结构提供了对阴离子电导基础的深入了解。
The naturally occurring channelrhodopsin variant anion channelrhodopsin-1 (ACR1), discovered in the cryptophyte algae Guillardia theta, exhibits large light-gated anion conductance and high anion selectivity when expressed in heterologous settings, properties that support its use as an optogenetic tool to inhibit neuronal firing with light. However, molecular insight into ACR1 is lacking owing to the absence of structural information underlying light-gated anion conductance. Here we present the crystal structure of G. theta ACR1 at 2.9 Å resolution. The structure reveals unusual architectural features that span the extracellular domain, retinal-binding pocket, Schiff-base region, and anion-conduction pathway. Together with electrophysiological and spectroscopic analyses, these findings reveal the fundamental molecular basis of naturally occurring light-gated anion conductance, and provide a framework for designing the next generation of optogenetic tools. The crystal structure of anion channelrhodopsin-1 (ACR1) from the algae Guillardia theta provides insights into the basis of anion conductance.
DOI: 10.1038/s41598-017-07363-w
发表时间: 2017-08-03
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影响因子: 4.6
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期刊: BIOCHEMISTRY
影响因子: 2.9
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影响因子: 4.6
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