9YDA
Cryo-EM structure of active human green cone opsin in complex with chimeric G protein (miniGist)
Summary for 9YDA
| Entry DOI | 10.2210/pdb9yda/pdb |
| EMDB information | 72798 |
| Descriptor | Medium-wave-sensitive opsin 1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total) |
| Functional Keywords | g protein-coupled receptor, cone opsin, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 172889.86 |
| Authors | |
| Primary citation | Yao, W.,Fay, J.F.,Farrens, D.L. Structure of human green cone opsin yields insights into mechanisms underlying the rapid decay of its active, signaling state. Proc.Natl.Acad.Sci.USA, 122:e2516318122-e2516318122, 2025 Cited by PubMed Abstract: Cone 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, ~100× 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) 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 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 Å of the Schiff base. Our biophysical assays show that neutralizing E102 (mutant GCO) slows retinal release (~8×) 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. These unique attributes in GCO 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. PubMed: 41329744DOI: 10.1073/pnas.2516318122 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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