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Publication Abstract from PubMed

Channelrhodopsins, light-gated cation channels, enable precise control of neural cell depolarization or hyperpolarization with light in the field of optogenetics. This study integrates time-resolved serial crystallography and atomistic molecular dynamics (MD) simulations to resolve the structural changes during C1C2 channelrhodopsin activation. Our observations reveal that within the crystal environment, C1C2 predominantly remains in a light-activated state with characteristics of the M(390) intermediate. Here, rearrangement of retinal within its binding pocket partially opens the central gate toward the extracellular vestibule. These structural changes initiate channel opening but were insufficient to allow K(+) flow. Adjusting protonation states to represent the subsequent N(520) intermediate in our MD simulations induced further conformational changes, including rearrangements of transmembrane helices 2 and 7, that opened the inner gate and the putative ion-translocation pathway. This allowed spontaneous cation conduction with low conductance, aligning with experimental findings. Our findings provide critical structural insights into key intermediates of the channel opening mechanism, enhancing our understanding of ion conduction and selectivity in channelrhodopsins at an atomistic level.

Structural Insights Into the Opening Mechanism of C1C2 Channelrhodopsin.,Mulder M, Hwang S, Broser M, Brunle S, Skopintsev P, Schattenberg C, Schnick C, Hartmann S, Church J, Schapiro I, Dworkowski F, Weinert T, Hegemann P, Sun H, Standfuss J J Am Chem Soc. 2025 Jan 8;147(1):1282-1290. doi: 10.1021/jacs.4c15402. Epub 2024 , Dec 16. PMID:39680650^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.