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Extending the Structural View of Class B GPCRs.

de Graaf, Chris; Song, Gaojie; Cao, Can; Zhao, Qiang; Wang, Ming-Wei; Wu, Beili; Stevens, Raymond C.
Trends Biochem Sci; 42(12): 946-960, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29132948
The secretin-like class B family of G protein-coupled receptors (GPCRs) are key players in hormonal homeostasis. Recent structures of various receptors in complex with a variety of orthosteric and allosteric ligands provide fundamental new insights into the function and mechanism of class B GPCRs, including: (i) ligand-induced changes in the relative orientation of the extracellular and transmembrane receptor domains; (ii) intramolecular interaction networks that stabilize conformational changes to accommodate intracellular G protein binding; and (iii) allosteric modulation of receptor activation. This review provides a comprehensive analysis of the structural, biochemical, and pharmacological data on class B GPCRs for understanding ligand-receptor interaction and modulation mechanisms and assessing the potential implications for drug discovery for the secretin-like GPCR family.
Selo DaSilva