Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization.
Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization.
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DOI：
10.1038/s41467-020-20596-0
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发表时间：
2021-01-27
影响因子：
16.6
通讯作者：
Watts A
中科院分区：
文献类型：
--
作者：
Bada Juarez JF;Judge PJ;Adam S;Axford D;Vinals J;Birch J;Kwan TOC;Hoi KK;Yen HY;Vial A;Milhiet PE;Robinson CV;Schapiro I;Moraes I;Watts A
许多跨膜受体处于脱敏状态，不能对外界刺激做出反应。微生物视紫红质蛋白家族包括这样一组受体，其不活跃或暗适应(DA)状态是在长时间无光的情况下建立的。在这里，我们给出了Ar3的基态(光适应)和DA态的高分辨晶体结构，分别解算到1.1 ？和1.3 ？我们观察到这两个状态在水分子的动力学上的显着差异，水分子通过氢键连接到视网膜Schiff碱。支持QM/MM计算揭示了DA状态如何允许建立视网膜异构体之间的热力学平衡，以及在没有光的情况下如何在基态阻止这种相同的变化。我们认为，与同系物相比，AR3内部水网络的不同排列是导致较快的光循环动力学的原因。古紫红质-3(AR3)突变体在光遗传学中被广泛用于神经元沉默和膜电压传感。高分辨晶体结构表明，当内部氢键水网络被修饰以响应生色团异构化的变化时，AR3光感受器发生减敏。
Many transmembrane receptors have a desensitized state, in which they are unable to respond to external stimuli. The family of microbial rhodopsin proteins includes one such group of receptors, whose inactive or dark-adapted (DA) state is established in the prolonged absence of light. Here, we present high-resolution crystal structures of the ground (light-adapted) and DA states of Archaerhodopsin-3 (AR3), solved to 1.1 Å and 1.3 Å resolution respectively. We observe significant differences between the two states in the dynamics of water molecules that are coupled via H-bonds to the retinal Schiff Base. Supporting QM/MM calculations reveal how the DA state permits a thermodynamic equilibrium between retinal isomers to be established, and how this same change is prevented in the ground state in the absence of light. We suggest that the different arrangement of internal water networks in AR3 is responsible for the faster photocycle kinetics compared to homologs. Archaerhodopsin-3 (AR3) mutants are commonly used in optogenetics for neuron silencing and membrane voltage sensing. High-resolution crystal structures show that desensitization of the AR3 photoreceptor occurs when internal hydrogen-bonded water networks are modified in response to changes in chromophore isomerization.
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影响因子：
62.1
作者：
Ernst, Oliver P.;Lodowski, David T.;Elstner, Marcus;Hegemann, Peter;Brown, Leonid S.;Kandori, Hideki
通讯作者：
Kandori, Hideki
影响因子：
13.9
作者：
Fenno L;Yizhar O;Deisseroth K
通讯作者：
Deisseroth K
影响因子：
3.7
作者：
Adam S;Bondar AN
通讯作者：
Bondar AN
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3.8
作者：
Caffrey, Martin
通讯作者：
Caffrey, Martin