3.E.1.7.10
Kalium (potassium) channelrhodoopsin 1, KCR1, of 265 aas and 7 TMSs.  It shows higher selectivity for K⁺ than for Na⁺ and therefore is used to silence neurons with light (optogenetics). Replacement of the conserved cysteine residue in the TMS 3 (Cys110) with alanine or threonine results in a >1,000-fold decrease in the channel closing rate (Sineshchekov et al. 2023). Morizumi et al. 2025 single-particle cryo-EM to determine the structures of the slow-cycling mutant C110A of kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) in the dark and upon laser flash excitation. Upon photoisomerization of the retinal chromophore, the retinylidene Schiff base NH-bond reorients from the extracellular to the cytoplasmic side. This switch triggers a series of side chain reorientations and merges intramolecular cavities into a transmembrane K⁺ conduction pathway. Molecular dynamics simulations confirmed K⁺ flux through the illuminated state but not through the resting state. The overall displacement between the closed and the open structure is small, involving mainly side chain rearrangements. Asp105 and Asp116 play key roles in K⁺ conductance. Structure-guided mutagenesis and patch-clamp analysis revealed the roles of the pathway-forming residues in channel gating and selectivity (Morizumi et al. 2025).  Kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) was the first discovered natural light-gated ion channel showing higher selectivity to K⁺ than to Na⁺ and therefore is used to silence neurons with light (optogenetics). Replacement of the conserved cysteine residue in the transmembrane helix 3 (Cys110) with alanine or threonine results in a >1,000-fold decrease in the channel closing rate (Sineshchekov et al. 2024).