Lehrstuhl für Biophysik, Ruhr Universität Bochum, Universitätsstrasse 150, 44780 Bochum (Germany).
Angew Chem Int Ed Engl. 2015 Apr 13;54(16):4953-7. doi: 10.1002/anie.201410180. Epub 2014 Dec 23.
Channelrhodopsins (ChRs) are light-gated ion channels that are widely used in optogenetics. They allow precise control of neuronal activity with light, but a detailed understanding of how the channel is gated and the ions are conducted is still lacking. The recent determination of the X-ray structural model in the closed state marks an important milestone. Herein the open state structure is presented and the early formation of the ion conducting pore is elucidated in atomic detail using time-resolved FTIR spectroscopy. Photo-isomerization of the retinal-chromophore causes a downward movement of the highly conserved E90, which opens the pore. Molecular dynamic (MD) simulations show that water molecules invade through this opened pore, Helix 2 tilts and the channel fully opens within ms. Since E90 is a highly conserved residue, the proposed E90-Helix2-tilt (EHT) model might describe a general activation mechanism and provides a new avenue for further mechanistic studies and engineering.
通道视紫红质（ChR）是光门控离子通道，广泛用于光遗传学。它们允许用光精确控制神经元活动，但通道门控和离子传导的详细机制仍不清楚。最近确定的关闭状态下的 X 射线结构模型标志着一个重要的里程碑。本文呈现了开放状态的结构，并使用时间分辨傅里叶变换红外光谱法以原子细节阐明了离子传导孔的早期形成。视黄醛发色团的光异构化导致高度保守的 E90 向下移动，从而打开孔。分子动力学（MD）模拟表明，水分子通过这个打开的孔侵入，螺旋 2 倾斜，通道在毫秒内完全打开。由于 E90 是高度保守的残基，因此所提出的 E90-螺旋 2 倾斜（EHT）模型可能描述了一般的激活机制，并为进一步的机制研究和工程设计提供了新途径。
