Gated electron transport in rhodopsin and its relevance to GPCR activation

Abstract

We iden4fy, by density-func4onal theory calcula4ons, an electron donor-bridge-acceptor (DBA) complex within the highest resolu4on X-ray diffrac4on structures of rhodopsin. The donor is a conserved tryptophan, the acceptor is a zinc ion surrounded by a tryptophan, a his4dine and a conserved glutamate. The unusual environment of the zinc ion confers high electron affinity on the zinc site. The bridge is the re4nal which can exist either in the neutral aldimine (Schiff's base) or aldiminium (protonated) state. When the re4nal is unprotonated, no electron transfer occurs. Upon protona4on of the aldimine, the DBA complex conducts and a full electron charge is transferred from donor tryptophan to the zinc complex. This gated electron transfer creates the molecular equivalent of a tunnel triode. Since rhodopsin is the ancestor of GPCRs, we discuss the possible relevance of this gated electron transport to other GPCRs, in par4cular to olfactory receptors which have been proposed to use an electron tunneling mechanism to detect molecular vibra4ons.

Quantum effects in the brain: A review

“…On the subject of neurotransmitters, they hypothesise that the anomalous binding structure of the antagonist metitepine to serotonin related receptors can be explained if the metitepine is in the form of a radical, having gained an electron in binding to the receptor. This mechanism is in line with the idea that GPCRs are electronic devices rather than simply lock-and-key 104 .…”

“…GPCRs play an important role in medical innovation, as targets for drug action 103 . In addition to neurotransmitters, there are a number of biological molecules that bind to GPCRs; these include odourants 104 . Olfaction is classically understood as depending on the respective shapes of the chemical/receptor pair.…”

Spontaneous radiofrequency emission from electron spins within Drosophila: a novel biological signal

“…Note that these two possibilities are not mutually exclusive: there is much evidence connecting the still mysterious action of general anesthetics to mitochondrial function (Eckenhoff & Johansson, 1997;Hoppel, Sedensky -: The Journal of …, & 2002, 2002Morgan, Sedensky -The Journal of, & 1999, 1999Woll, Dailey, & Eckenhoff, 2018) . Our previous work on olfaction has established a connection between electron currents, odorant sensing and G-protein activation more generally (Franco, Turin, Mershin, & Skoulakis, 2011;Gane et al, 2013;Gehrckens, Horsfield, Skoulakis, & Turin, 2019;Horsfield, Haase, & Turin, 2017;L. Turin, 1996) , while that on general anesthesia has shown a correlation between spin content of Drosophila (as measured by CW ESR) and general anesthetic action (L. Luca Turin, Skoulakis, & Horsfield, 2014b) .…”

Evidence for Free Radical Drug Ligands in class A G-protein Coupled Receptors

“…If electrons move within Class A GPCRs, what is their impact on receptor function? In rhodopsin, the presence of delocalised orbitals due to the zinc alters the light absorption spectrum and may be used in tuning receptors to different wavelengths 9 . In other GPCRs the well-documented modulation of binding and response seen with dithiol reagents [20][21][22][23][24][25] is an indication of the functional significance of a redox pathway.…”

“…The conformation of methiothepin in 6wh4 is very close to the calculated closed-shell cation structure. In light of the electron transfer proposed in rhodopsin 9 , and given that the methiothepin cation contains both delocalised bonds and a positive charge, we wondered whether these two structures represented respectively the cation and the neutral free radical, i.e. whether adding an electron to the 6wh4 structure to give the neutral free radical would yield the 5v54 structure.…”