9yda
Cryo-EM structure of active human green cone opsin in complex with chimeric G protein (miniGist)
Structural highlights
DiseaseOPSG_HUMAN Blue cone monochromatism;Cone rod dystrophy;X-linked cone dysfunction syndrome with myopia. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. FunctionOPSG_HUMAN Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to cis-retinal.[1] [2] [3] Publication Abstract from PubMedCone opsins enable daylight vision and color discrimination. Like their dim-light cousin rhodopsin (Rho) found in rod cells, they use a covalently attached retinal ligand to sense light and initiate visual phototransduction by activating G proteins. Unfortunately, we know less about their structural properties, in part because their activated state is unstable-cone opsins release their retinal agonist within seconds after light activation, ~100x faster than Rho. To determine what causes this rapid release and how it affects G protein activation, we solved the structure of active-state, wild-type human green cone opsin (GCO(WT)) stabilized with a mini-G protein and then compared its structural and biophysical properties to Rho. Our results reveal unique features in the active-state GCO(WT) structure. These include i) a larger water channel connected to a larger retinal binding cavity, ii) a larger "hole" near the retinal Schiff base that could facilitate both retinal escape and water access; and iii) a potential anionic residue, E102, that lies within ~3.6 A of the Schiff base. Our biophysical assays show that neutralizing E102 (mutant GCO(E102Q)) slows retinal release (~8x) from the receptor and increases G protein activation. Surprisingly, our kinetic studies suggest that entropic factors are the main cause for the faster retinal release from activated GCO(WT). These unique attributes in GCO(WT) likely facilitate its function in bright daylight. These results support the proposal that rapid retinal release from an active-state cone opsin helps prevent signal saturation and enables rapid resetting of the receptor. Structure of human green cone opsin yields insights into mechanisms underlying the rapid decay of its active, signaling state.,Yao W, Fay JF, Farrens DL Proc Natl Acad Sci U S A. 2025 Dec 9;122(49):e2516318122. doi: , 10.1073/pnas.2516318122. Epub 2025 Dec 2. PMID:41329744[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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