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• W2041566506 abstract "In the G-protein-coupled receptor (GPCR) rhodopsin, the inactivating ligand 11-cis-retinal is bound in the seven-transmembrane helix (TM) bundle and is cis/trans isomerized by light to form active metarhodopsin II. With metarhodopsin II decay, all-trans-retinal is released, and opsin is reloaded with new 11-cis-retinal. Here we present the crystal structure of ligand-free native opsin from bovine retinal rod cells at 2.9 ångström (Å) resolution. Compared to rhodopsin, opsin shows prominent structural changes in the conserved E(D)RY and NPxxY(x)5,6F regions and in TM5–TM7. At the cytoplasmic side, TM6 is tilted outwards by 6–7 Å, whereas the helix structure of TM5 is more elongated and close to TM6. These structural changes, some of which were attributed to an active GPCR state, reorganize the empty retinal-binding pocket to disclose two openings that may serve the entry and exit of retinal. The opsin structure sheds new light on ligand binding to GPCRs and on GPCR activation. The G-protein-coupled receptors (GPCRs), or seven-transmembrane receptors, constitute one of the largest superfamilies in the human genome, and are a common target for therapeutics. The light-activated molecule rhodopsin is made up of a GPCR called opsin, with a central pocket containing a covalently bound photoreactive cofactor, retinal. Ligand-free GPCRs are notoriously difficult to purify, but Park et al. have succeeded in crystallizing native opsin from bovine retinal rod cells and determined its structure to 2.9Å resolution. The structure reveals an entrance pathway for 11-cis-retinal and an exit for all-trans-retinal, an example of the biologically important process of GPCR activation in action. The crystal structure of a ligand-free opsin at 2.9 Å resolution is reported; the entrance pathway for 11-cis-retinal and the exit pathway for all-trans-retinal are apparent." @default.
• W2041566506 created "2016-06-24" @default.
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• W2041566506 date "2008-06-18" @default.
• W2041566506 modified "2023-10-12" @default.
• W2041566506 title "Crystal structure of the ligand-free G-protein-coupled receptor opsin" @default.
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• W2041566506 doi "https://doi.org/10.1038/nature07063" @default.
• W2041566506 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18563085" @default.
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