Bacteriorhodopsin-like channelrhodopsins: Alternative mechanism for control of cation conductance

Significance Two well-characterized carboxylate residues catalyze vectorial proton transport in rhodopsin proton pumps, such as bacteriorhodopsin. We report the mechanism of a type of rhodopsin, a channelrhodopsin unique in that it exploits the same residues to accomplish a completely different process: opening and closing of a cation channel. This finding promises leaps in our understanding of how evolution modifies shared protein scaffolds to create new protein chemistry in homologous membrane proteins. Moreover, algal channelrhodopsins have become widespread molecular tools to manipulate membrane potential in cells with light (optogenetics). The structurally distinct, independently evolved channelrhodopsins studied here open the possibility for discovery of optogenetic tools with new properties. Our results provide insights into the conductance mechanisms of these channelrhodopsins.