Light-Induced Movement of the Transmembrane Helix B in Channelrhodopsin-2

摘要

In the past decade, its versatile usage has established charmelrhodopsin-2 (ChR2) as the most prominent opto-genetic tool. The precise spatio-temporal control of the activity of a neuron by light allows noninvasive in vitro or in vivo investigations of neural circuits. The key is the heterologous expression of ChR2, a member of the type-I rhodopsins, that enters a photocycle upon light activation starting with the isomerization around the C13-C14 bond of its chromophore retinal. The intermediates of the photo-cycle are linked to a closed and an open state of an ion pore. Cation flux during the open state depolarizes the cell membrane thereby triggering neuronal action potentials. A coupling of isomerization with structural alterations is well-known for bacteriorhodopsin (bR) and sensory rhodopsi-n II (SRII) that eventually leads to movement of the cytoplasmic part of transmembrane helices (TMHs) F and G. Conformational changes are also anticipated for ChR2 propagating from the chromophore to the putative cation pore. According to a homology model of ChR2 and the closed state structure of a chimera (C1C2) of ChRl (TMHs A to E) and ChR2 (TMHs F and G), the pore comprises residues from TMHs A, B, C, and G, including a ChR characteristic patch of glutamate residues in TMH B.