Structural basis for ion selectivity and engineering in channelrhodopsins

[Display omitted] •Structural comparison between anion and cation conducting channelrhodopsins.•Structural comparison between channelrhodopsins and ligand-gated Cl−, K+, and Ca2+ channels.•Strategies for engineering Cl−, K+ and Ca2+ conducting channelrhodopsins.•Experimental options for determining open-state channelrhodopsin structures. Channelrhodopsins have become an integral part of modern neuroscience approaches due to their ability to control neuronal activity in targeted cell populations. The recent determination of several channelrhodopsin X-ray structures now enables us to study their function with unprecedented molecular precision. We will discuss how these insights can guide the engineering of the ion conducting pathway to increase its selectivity for Cl−, Ca2+, and K+ ions and improve the overall conductance. Engineering such channelrhodopsins would further increase their utility in neuroscience research and beyond by controlling a wider range of physiological events. To thoroughly address this issue, we compare channelrhodopsin structures with structural features of voltage and ligand-gated K+, Cl− and Ca2+ channels and discuss how these could be implemented in channelrhodopsins.