8fcz | pdb_00008fcz

Crystal structure of ground-state rhodopsin in complex with a nanobody

spinqualitylabelsall models 8fcz, resolution 3.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fcz is a 4 chain structure with sequence from Bos taurus and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.7Å Ligands: BMA, MAN, NAG, RET Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OPSD_BOVIN Photoreceptor required for image-forming vision at low light intensity. Required for photoreceptor cell viability after birth. Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change leading to G-protein activation and release of all-trans retinal (By similarity). Publication Abstract from PubMed Rhodopsin is a prototypical G protein-coupled receptor (GPCR) critical for vertebrate vision. Research on GPCR signaling states has been facilitated using llama-derived nanobodies (Nbs), some of which bind to the intracellular surface to allosterically modulate the receptor. Extracellularly binding allosteric nanobodies have also been investigated, but the structural basis for their activity has not been resolved to date. Here, we report a library of Nbs that bind to the extracellular surface of rhodopsin and allosterically modulate the thermodynamics of its activation process. Crystal structures of Nb2 in complex with native rhodopsin reveal a mechanism of allosteric modulation involving extracellular loop 2 and native glycans. Nb2 binding suppresses Schiff base deprotonation and hydrolysis and prevents intracellular outward movement of helices five and six - a universal activation event for GPCRs. Nb2 also mitigates protein misfolding in a disease-associated mutant rhodopsin. Our data show the power of nanobodies to modulate the photoactivation of rhodopsin and potentially serve as therapeutic agents for disease-associated rhodopsin misfolding. Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain.,Wu A, Salom D, Hong JD, Tworak A, Watanabe K, Pardon E, Steyaert J, Kandori H, Katayama K, Kiser PD, Palczewski K Nat Commun. 2023 Aug 25;14(1):5209. doi: 10.1038/s41467-023-40911-9. PMID:37626045 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Rhodopsin 3D structures

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