Department of Biochemistry and Molecular Biology, Center for Membrane Biology, University of Texas Health Science Center - McGovern Medical School, Houston, United States.
Swiss Light Source, Paul Scherrer Institute, Villigen, Switzerland.
Elife. 2019 Jan 7;8:e41741. doi: 10.7554/eLife.41741.
The anion channelrhodopsin ACR1 from the alga is a potent neuron-inhibiting optogenetics tool. Presented here, its X-ray structure at 2.9 Å reveals a tunnel traversing the protein from its extracellular surface to a large cytoplasmic cavity. The tunnel is lined primarily by small polar and aliphatic residues essential for anion conductance. A disulfide-immobilized extracellular cap facilitates channel closing and the ion path is blocked mid-membrane by its photoactive retinylidene chromophore and further by a cytoplasmic side constriction. The structure also reveals a novel photoactive site configuration that maintains the retinylidene Schiff base protonated when the channel is open. These findings suggest a new channelrhodopsin mechanism, in which the Schiff base not only controls gating, but also serves as a direct mediator for anion flux.
藻类来源的阴离子通道视紫红蛋白 ACR1 是一种强效的神经元抑制型光遗传学工具。本文呈现了其 2.9Å 的 X 射线结构，揭示了一条贯穿蛋白的隧道，从细胞外表面延伸到一个大的细胞质腔。隧道主要由小的极性和脂肪族残基排列而成，这些残基对阴离子传导至关重要。一个二硫键固定的细胞外帽促进了通道关闭，光活性视黄醛发色团在跨膜中段阻塞离子通道，进一步被细胞质侧缩窄所阻断。该结构还揭示了一种新的光活性位点构象，当通道打开时，视黄醛席夫碱保持质子化。这些发现提出了一种新的通道视紫红蛋白机制，其中席夫碱不仅控制门控，还作为阴离子流的直接介体。
