Rhodopsin - the RHO protein

MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVLGGFTSTLYTSLHGYFVFGPTGCNLEGFFATLGGEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLAGWSRYIPEGLQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIIIFFCYGQLVFTVKEAAAQQQESATTQKAEKEVTRMVIIMVIAFLICWVPYASVAFYIFTHQGSNFGPIFMTIPAFFAKSAAIYNPVIYIMMNKQFRNCMLTTICCGKNPLGDDEASATVSKTETSQVAPA

Figure 5: the primary structure of rhodopsin, where each letter represents a specific amino acid. Highlighted in blue are the transmembrane domain boundaries.

Primary structure

Figure 1 displays the primary structure of rhodopsin, comprised of 348 amino acids, with the N terminal region of the protein at the beginning of the sequence, and the C terminal region at the end. Highlighted in blue are the transmembrane helix domain boundaries of the protein.

Secondary structure

The secondary structure of a protein is characterised by the alpha helices and beta pleated sheets. In figure 6, the rhodopsin protein monomer is composed of seven transmembrane helix cores, which are highlighted in red. 237 amino acids contribute to alpha helices. Two beta sheets are also present from Gly4 to Pro11, and are highlighted in yellow in figure 7. 10 amino acids contribute to the beta sheets of rhodopsin’s secondary structure.

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Tertiary structure

The tertiary structure includes a combination of alpha helices and beta sheets, along with other structures such as loops, visible in figure 10. Three loop structures are present on each side of the protein, with loops therefore being present on the cytoplasmic and extracellular regions of the protein. Loops also follow secondary structures, for example the 24 amino acid loop that follows the beta sheets. The surface composition of the tertiary structure is shown in figure 9.

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Quaternary structure

The quaternary structure forms when multiple subunits come together to contribute to the function of the protein. Rhodopsin is able to function as a homodimer, in which two rhodopsin proteins interact with each other to form a complex made of two identical protein subunits. The green and blue regions in figures 11 and 12 represent each rhodopsin monomer interacting to form a homodimer via hydriophobic interactions.

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Watch the video below to learn more about the 3D structure of Rhodopsin.

Rhodopsin: structure and function

Rhodopsin is a transmembrane protein (1), with a cytosolic region, membrane-embedded region and an interdiscal region (2). Figure 12 shows the placement of rhodopsin as a transmembrane protein within rod cells. The extracellular, or interdiscal, loops of rhodopsin are involved in protein stability and binding of ligands to the GPCR. The position of the beta sheets allows for a pocket to be formed that facilitates the binding of the ligand, and ensures that the ligand is not released from the protein too early (3). Rhodopsin has the ability to undergo a conformational change when it is exposed to photons and activated. When photons interact with rhodopsin, the cytoplasmic region of the protein (helix 6) is pushed away from the rest of the transmembrane helices through the breaking of ionic bonds, changing the hydrophobic interactions between residues and creating a binding site in the cytoplasmic region for the G protein transducin, which faciliates the conversion of GDP to GTP, allowing for visual processing.

Figure 12: the positioning of the functional rhodopsin protein within the retinal membrane, with the cytoplasmic, transmembrane, and interdiscal (extracellular) regions labelled. The 7 transmembrane helices are labelled with the letters A-G.

References:

1. Hwa J, Garriga P, Liu X, Khorana HG. Structure and function in rhodopsin: Packing of the helices in the transmembrane domain and folding to a tertiary structure in the intradiscal domain are coupled. Proceedings of the National Academy of Sciences. 1997;94(20):10571–6. doi:10.1073/pnas.94.20.10571

2. Palczewski K. G protein–coupled receptor rhodopsin. Annual Review of Biochemistry. 2006;75(1):743–67. doi:10.1146/annurev.biochem.75.103004.142743

3. Zhou XE, Melcher K, Xu HE. Structure and activation of rhodopsin. Acta Pharmacologica Sinica. 2012;33(3):291–9. doi:10.1038/aps.2011.171