Modulation of Light Energy Transfer from Chromophore to Protein in the Channelrhodopsin ReaChR

Abstract

The function of photoreceptors relies on efficient transfer of absorbed light energy from the chromophore to the protein to drive conformational changes that ultimately generate an output signal. In retinal-binding proteins, mainly two mechanisms exist to store the photon energy after photoisomerization: 1) conformational distortion of the prosthetic group retinal, and 2) charge separation between the protonated retinal Schiff base (RSBH þ ) and its counterion complex. Accordingly, energy transfer to the protein is achieved by chromophore relaxation and/or reduction of the charge separation in the RSBH þ -counterion complex. Combining FTIR and UV-Vis spectroscopy along with molecular dynamics simulations, we show here for the widely used, red-activatable Volvox carteri channelrhodopsin-1 derivate ReaChR that energy storage and transfer into the protein depends on the protonation state of glutamic acid E163 (Ci1), one of the counterions of the RSBH þ . Ci1 retains a pK a of 7.6 so that both its protonated and deprotonated forms equilibrate at physiological conditions. Protonation of Ci1 leads to a rigid hydrogenbonding network in the active-site region. This stabilizes the distorted conformation of the retinal after photoactivation and decelerates energy transfer into the protein by impairing the release of the strain energy. In contrast, with deprotonated Ci1 or removal of the Ci1 glutamate side chain, the hydrogen-bonded system is less rigid, and energy transfer by chromophore relaxation is accelerated. Based on the hydrogen out-of-plane (HOOP) band decay kinetics, we determined the activation energy for these processes in dependence of the Ci1 protonation state.

Evolution of the Automatic Rhodopsin Modeling (ARM) Protocol

“…Furthermore, a residue may be present as an equilibrium between ionized and not-ionized forms, hence carrying only a partial charge. These issues are a current research matter [35,[71][72][73].…”

“…Note that in QM/MM modeling, it is a common practice to evaluate the protonation states of the rPSB counterion complex by looking, as a guide, at the reproducibility of the experimental a max (see, for instance, Refs. [35,[71][72][73]) Indeed, the novelty of the default and customized approaches is that, regardless of the user or computational facility, reproducible inputs, and consequently reproducible ARM QM/MM model s, are guaranteed when the same parameters are used. This represents an advancement with respect to the original version since it allows for the models to be reproduced in any laboratory and by any user, even when starting building an ARM QM/MM model from scratch (see point (3) of Sect.…”

“…Note that in QM/MM modeling, it is a common practice to evaluate the protonation states of the counterion complex by looking, as a guide, at the reproducibility of the experimental (see, for instance, Refs. [ 35 , 71 – 73 ])…”

Recent advances in low-level laser therapy on depression

“…The pigments in the rods and three types of cones turn retinal to absorb a specific wavelength of light [19]. The photon absorption results in the isomerization of retinal from the 11-cis to the all-trans conformation and triggers a conformational change in the protein that initiates a cascade of events in the cell [20,21]. Cyclic nucleotide-gated ion channels are closed, and the release of synaptic transmitters is inhibited by membrane potential hyperpolarization.…”