Structural mechanisms of selectivity and gating in anion channelrhodopsins.
Structural mechanisms of selectivity and gating in anion channelrhodopsins.
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DOI：
10.1038/s41586-018-0504-5
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发表时间：
2018-09
期刊：
影响因子：
64.8
通讯作者：
Deisseroth K
中科院分区：
文献类型：
--
作者：
Kato HE;Kim YS;Paggi JM;Evans KE;Allen WE;Richardson C;Inoue K;Ito S;Ramakrishnan C;Fenno LE;Yamashita K;Hilger D;Lee SY;Berndt A;Shen K;Kandori H;Dror RO;Kobilka BK;Deisseroth K
设计的和天然的阴离子传导通道视紫红质（分别为dACR和nACR）已广泛应用于光遗传学（在动物行为研究期间选择性抑制靶细胞活性），但每一类都表现出性能限制，强调了通道结构-功能关系的权衡。因此，对dACRs和nACRs的分子和结构见解不仅对于理解这些光门控阴离子通道的基本机制至关重要，而且对于创建下一代光遗传学工具也至关重要。在这里，我们报告的dACR iC++的晶体结构，沿着与光谱，电生理和计算分析，提供意想不到的见解pH值依赖性，底物识别，通道门控和离子选择性的dACR和nACR。这些结果使我们能够创建一个阴离子传导通道视紫红质集成的主要特点，大的光电流和快速动力学以及独家阴离子选择性。
Both designed and natural anion-conducting channelrhodopsins (dACRs and nACRs, respectively) have been widely applied in optogenetics (enabling selective inhibition of target-cell activity during animal behaviour studies), but each class exhibits performance limitations, underscoring trade-offs in channel structure-function relationships. Therefore, molecular and structural insights into dACRs and nACRs will be critical not only for understanding the fundamental mechanisms of these light-gated anion channels, but also to create next-generation optogenetic tools. Here we report crystal structures of the dACR iC++, along with spectroscopic, electrophysiological and computational analyses that provide unexpected insights into pH dependence, substrate recognition, channel gating and ion selectivity of both dACRs and nACRs. These results enabled us to create an anion-conducting channelrhodopsin integrating the key features of large photocurrent and fast kinetics alongside exclusive anion selectivity.
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影响因子：
64.8
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
通讯作者：
Deisseroth K
影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
4.6
作者：
Govorunova EG;Sineshchekov OA;Rodarte EM;Janz R;Morelle O;Melkonian M;Wong GK;Spudich JL
通讯作者：
Spudich JL
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH