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Nature:KR2 光驱动钠离子泵结构

摘要 : 在来自海洋细菌Krokinobacter eikastus的一个光驱动的能够泵浦钠离子的视紫红质最近被发现之前,已知的微生物视紫红质被分成两类:向外的质子泵或向内的氯化物泵。

在来自海洋细菌Krokinobacter eikastus的一个光驱动的能够泵浦钠离子的视紫红质最近被发现之前,已知的微生物视紫红质被分成两类:向外的质子泵或向内的氯化物泵。被称为KR2的这一新蛋白作为用于光遗传学研究的一个潜在工具正在引起关注:它的激活会改变一个目标细胞的钠离子浓度,而不只是pH值或氯化物浓度。现在,Osamu Nureki及同事获得了KR2的两个X-射线晶体结构,并用它们来提出关于钠离子运输的一个工作模型。基于这些结构,本文作者设计了KR2的几个突变体,并且成功地做成了一个钾离子运输泵。


Structural basis for Na+ transport mechanism by a light-driven Na+ pump


Krokinobacter eikastus rhodopsin 2 (KR2) is the first light-driven Na+ pump discovered, and is viewed as a potential next-generation optogenetics tool. Since the positively charged Schiff base proton, located within the ion-conducting pathway of all light-driven ion pumps, was thought to prohibit the transport of a non-proton cation, the discovery of KR2 raised the question of how it achieves Na+ transport. Here we present crystal structures of KR2 under neutral and acidic conditions, which represent the resting and M-like intermediate states, respectively. Structural and spectroscopic analyses revealed the gating mechanism, wherby the flipping of Asp116 sequesters the Schiff base proton from the conducting pathway to facilitate Na+ transport. Together with the structure-based engineering of the first light-driven K+ pumps, electrophysiological assays in mammalian neurons and behavioural assays in a nematode, our studies reveal the molecular basis for light-driven non-proton cation pumps and thus provide a framework that may advance the development of next-generation optogenetics.

来源: Nature 浏览次数:0


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