Protein domains and interactions

Figure 13: Rhodopsin protein within the plasma membrane, highlighting the location of the N and C terminals.

Rhodopsin protein domains

Rhodopsin possesses domains associated with GCPRs, including a seven transmembrane helix domain region, which allows for stability in the retinal membrane, alongside facilitating conformational changes that confer the activity of rhodopsin (1). Within this transmembrane region is the ligand binding domain (2), which allows for the interaction between rhodopsin and its ligands. The cytosolic and interdiscal domains of rhodopsin are associated with maintaining the structural conformation of rhodospin, and facilitiating protein-protein and protein-ligand interactions.

Figure 14: Rhodopsin monomer, with the locations of the zinc ion binding sites labelled with the blue arrows.

Protein-ligand interactions

Analysis via BioLip: https://zhanggroup.org/BioLiP/qsearch.cgi

Zinc ions (Zn2+)

Zinc has the ability to allosterically modulate the structure and function of rhodopsin, as it is able to interact with many GPCRs because of their similar structure (3).
Zinc binding facilitates the stability of rhodopsin in low light conditions, assists in binding of other ligands such as retinal (4), and is involved in transforming rhodopsin to the active form metarhodopsin II.

11-cis retinal

Located within a rhodopsin chromophore, 11-cis retinal antagonises rhodopsin to keep it in an off state when it is not needed (in brightly lit conditions) (5). The chromophore structure is located within the centre of the rhodopsin protein.
Photochemical activity chemically manipulates the chromophore and changes the retinal molecular composition, allowing rhodopsin to be activated.

Protein-protein interactions

Analysis via STRING: https://string-db.org/cgi/network?taskId=bydrblbc5ua0&sessionId=bJpITyEaw6Du

The STRING predicted proteins with the strongest functional relationships to rhodopsin include:

Guanine-nucleotide-binding protein subunit alpha 1 (GNAT1): facilitates signal transduction for rhodopsin in rod photoreceptors.
Rhodopsin kinase GRK7 and GRK1: turns off photoreceptors in different light conditions - for example, represses rod functionality in bright light.
S-arrestin (SAG): competitively binds to RHO to terminate RHO signalling G-proteins.

Figure 15: STRING analysis output for protein-protein interactions with homo sapien rhodopsin and the proteins it most commonly interacts with. Each node represents a different protein, with lines representing interactions between proteins, indicating that they have a shared function or interact with one another physically or chemically.

References:

1. Hilger D, Masureel M, Kobilka BK. Structure and dynamics of GPCR signaling complexes. Nature Structural & Molecular Biology. 2018;25(1):4–12. doi:10.1038/s41594-017-0011-7

2. Murray AR, Fliesler SJ, Al-Ubaidi MR. Rhodopsin: The functional significance of ASN-linked glycosylation and other post-translational modifications. Ophthalmic Genetics. 2009;30(3):109–20. doi:10.1080/13816810902962405

3. Shuster TA, Martin F, Nagy AK. Zinc causes an apparent increase in rhodopsin phosphorylation. Current Eye Research. 1996;15(10):1019–24. doi:10.3109/02713689609017650

4. Stojanovic A, Stitham J, Hwa J. Critical role of transmembrane segment zinc binding in the structure and function of rhodopsin. Journal of Biological Chemistry. 2004;279(34):35932–41. doi:10.1074/jbc.m403821200

5. Kono M, Goletz PW, Crouch RK. 11-cis- and all-trans-retinols can activate rod opsin: Rational design of the visual cycle. Biochemistry. 2008;47(28):7567–71. doi:10.1021/bi800357b

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