小柯机器人

澳大利亚悉尼大学Renae M. Ryan等研究人员合作发现，谷氨酸转运蛋白具有带有两个疏水通道的氯离子通道。这一研究成果于2021年2月17日在线发表在国际学术期刊《自然》上。

研究人员报道了谷氨酸转运蛋白同系物在开放通道状态下的冷冻电镜结构，该结构揭示了在谷氨酸转运周期中形成的水腔。该腔的功能特性与分子动力学模拟相结合，揭示出它是一种水可及的氯离子渗透途径，该途径由两个疏水区域控制，并且在哺乳动物和古细菌谷氨酸转运蛋白中均保守。这些发现提供了对谷氨酸转运蛋白支持其双重功能机制的见解，并提供了有助于解析由可溶性载体1A转运蛋白家族共享的完整转运周期的信息。 

据了解，谷氨酸是中枢神经系统中最丰富的兴奋性神经递质，其精确控制对于维持正常的脑功能和防止兴奋性毒性至关重要。细胞外谷氨酸的去除是通过血浆膜结合的转运蛋白实现的，该转运蛋白利用升降机机制将谷氨酸的转运耦合到钠、钾和pH梯度上。谷氨酸转运蛋白还通过通道状过程传导氯离子，该过程在热力学上与转运过程脱钩。但是，使这些双功能转运蛋白能够发挥两个看似矛盾作用的分子机制尚不清楚。

附：英文原文

Title: Glutamate transporters have a chloride channel with two hydrophobic gates

Author: Ichia Chen, Shashank Pant, Qianyi Wu, Rosemary J. Cater, Meghna Sobti, Robert J. Vandenberg, Alastair G. Stewart, Emad Tajkhorshid, Josep Font, Renae M. Ryan

Issue&Volume: 2021-02-17

Abstract: Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and its precise control is vital to maintain normal brain function and to prevent excitotoxicity1. The removal of extracellular glutamate is achieved by plasma-membrane-bound transporters, which couple glutamate transport to sodium, potassium and pH gradients using an elevator mechanism2,3,4,5. Glutamate transporters also conduct chloride ions by means of a channel-like process that is thermodynamically uncoupled from transport6,7,8. However, the molecular mechanisms that enable these dual-function transporters to carry out two seemingly contradictory roles are unknown. Here we report the cryo-electron microscopy structure of a glutamate transporter homologue in an open-channel state, which reveals an aqueous cavity that is formed during the glutamate transport cycle. The functional properties of this cavity, combined with molecular dynamics simulations, reveal it to be an aqueous-accessible chloride permeation pathway that is gated by two hydrophobic regions and is conserved across mammalian and archaeal glutamate transporters. Our findings provide insight into the mechanism by which glutamate transporters support their dual function, and add information that will assist in mapping the complete transport cycle shared by the solute carrier 1A transporter family.

DOI: 10.1038/s41586-021-03240-9

Source: https://www.nature.com/articles/s41586-021-03240-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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