Opening Ion-Transfer Paths of Channelrhodopsin

Abstract

The light-driven reaction cycle of channelrhodopsin involves coupling between proton-transfer reactions, water and protein dynamics. In the resting state of the channel, the retinal chromophore is all-trans and the ion-conducting channel is closed. Upon photoisomerization of the retinal to 13-cis, a reaction cycle is triggered during which a cation channel opens, and the retinal Schiff base and specific carboxylate groups participate in proton transfers. A key open question concerns the location and dynamics of internal water molecules that could participate in proton transfers, or assist the passage of cations. We address this question by performing extensive all-atom molecular dynamics simulations of wild-type channelrhodopsin-2 from C. reinhardtii modeled in all-trans vs. 13-cis retinal states. We find that isomerization of the retinal chromophore results in a marked redistribution of water molecules, including close to protein groups thought to participate directly in proton transfer reactions. This work was supported in part by the DFG Collaborative Research Center SFB 1078 ‘Protonation dynamics in Protein Function’ Projects B3 (to J.H.) and C4 (to A.-N.B.), and by the HLRN, the North-German Supercomputing Alliance (bec00063, to A.-N.B.).