Structures of the glucocorticoid-bound adhesion receptor GPR97–Go complex
نویسندگان
چکیده
Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge their ligand regulation or structure is available1–3. Here we report that glucocorticoid stress hormones activate adhesion receptor G3 (ADGRG3; also known as GPR97)4–6, prototypical GPCR. The cryo-electron microscopy structures GPR97–Go complexes bound to the anti-inflammatory drug beclomethasone steroid hormone cortisol revealed glucocorticoids bind pocket within transmembrane domain. steroidal core packed against ‘toggle switch’ residue W6.53, which senses binding and induces activation receptor. Active GPR97 uses quaternary HLY motif fasten seven-transmembrane bundle mediate G protein coupling. cytoplasmic side has an open cavity, where all three intracellular loops interact with Go protein, contributing high basal activity GRP97. Palmitoylation at cytosolic tail was found be essential for efficient engagement not observed in other solved GPCR complex structures. Our work provides structural basis domain subsequent authors on glucocorticoid-bound receptor–G complex.
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ژورنال
عنوان ژورنال: Nature
سال: 2021
ISSN: ['1476-4687', '0028-0836']
DOI: https://doi.org/10.1038/s41586-020-03083-w