Coupling of Protonation Switches During Rhodopsin Activation†: Photochemistry and Photobiology, 2007, 83
Open accessAbstract
Recent studies of the activation mechanism of rhodopsin involving Fourier-transform infrared spectroscopy and a combination of chromophore modifications and site-directed mutagenesis reveal an allosteric coupling between two protonation switches. In particular, the ring and the 9-methyl group of the all-trans retinal chromophore serve to couple two proton-dependent activation steps: proton uptake by a cytoplasmic network between transmembrane (TM) helices 3 and 6 around the conserved ERY (Glu-Arg-Tyr) motif and disruption of a salt bridge between the retinal protonated Schiff base (PSB) and a protein counterion in the TM core of the receptor. Retinal analogs lacking the ring or 9-methyl group are only partial agonists--the conformational equilibrium between inactive Meta I and active Meta II photoproduct states is shifted to Meta I. An artificial pigment was engineered, in which the ring of retinal was removed and the PSB salt bridge was weakened by fluorination of C14 of the retinal polyene. These modifications abolished allosteric coupling of the proton switches and resulted in a stabilized Meta I state with a deprotonated Schiff base (Meta I(SB)). This state had a partial Meta II-like conformation due to disruption of the PSB salt bridge, but still lacked the cytoplasmic proton uptake reaction characteristic of the final transition to Meta II. As activation of native rhodopsin is known to involve deprotonation of the retinal Schiff base prior to formation of Meta II, this Meta I(SB) state may serve as a model for the structural characterization of a key transient species in the activation pathway of a prototypical G protein-coupled receptor.
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A switch in the counterion from Glu113 to Glu181 is believed to occur.
“it is believed that a switch in the counterion occurs from Glu113 to Glu181.”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [324]
The Introduction identifies Glu113 as the retinal Schiff-base counterion and says its salt bridge breaks during the Meta I–Meta II transition. Neither that passage nor the passages retrieved for “Glu181” say that Glu181 takes over as counterion, so the proposed switch is not supported by our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredRhodopsin is the main protein of ROS disk and plasma membranes, making up 90% and 75% of their protein content respectively.
“Rhodopsin is the main component of disk and plasma membranes of ROS, accounting for 90 and 75% of their protein content.”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [324]
The Introduction (page unavailable) identifies rhodopsin as a rod-cell visual pigment and describes experiments in native disk membranes. It does not state that rhodopsin is the main protein of either disk or plasma membranes, or give the claimed 90% and 75% figures. Searches for those percentages and for rod outer segment membrane abundance found no supporting passage. (LLM, conf=0.73)
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- Authors
- Vogel, R., Sakmar, T. P., Sheves, M., & Siebert, F.
- Affiliations
- University of Freiburg (DE)
- Rockefeller University (US)
- Weizmann Institute of Science (IL)
- Corresponding author
- Vogel, Reiner
- Venue
- Photochemistry and Photobiology
- Publisher
- American Society for Photobiology
- Published
- 2007-04-26
- Volume
- 83
- Issue
- 2
- Pages
- 286-292
- ISSN
- 0031-8655 (ISSN-L)
- OpenAlex
- W1519395209
- Cited by
- 34
- References
- 32
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 4
- FWCI
- 0.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Photochemistry and Photobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Ellison Medical Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Physical Sciences › Materials Science › Materials Chemistry › Photochromic and Fluorescence Chemistry
- Keywords
- rhodopsin activation, allosteric communication, retinal Schiff base, deprotonation, salt bridges, retinal analogs, G protein-coupled receptors, partial agonists, artificial pigments
- MeSH terms
- Allosteric Regulation, Animals, Binding Sites, Ligands, Models, Molecular, Photochemistry, Protons, Retinaldehyde, Rhodopsin, Schiff Bases, Mutagenesis, Site-Directed, In Vitro Techniques
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