8ibu
From Proteopedia
Cryo-EM structure of the erythromycin-bound motilin receptor-Gq protein complex
Structural highlights
FunctionGBB1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.[1] Publication Abstract from PubMedMotilin is an endogenous peptide hormone almost exclusively expressed in the human gastrointestinal (GI) tract. It activates the motilin receptor (MTLR), a class A G protein-coupled receptor (GPCR), and stimulates GI motility. To our knowledge, MTLR is the first GPCR reported to be activated by macrolide antibiotics, such as erythromycin. It has attracted extensive attention as a potential drug target for GI disorders. We report two structures of G(q)-coupled human MTLR bound to motilin and erythromycin. Our structures reveal the recognition mechanism of both ligands and explain the specificity of motilin and ghrelin, a related gut peptide hormone, for their respective receptors. These structures also provide the basis for understanding the different recognition modes of erythromycin by MTLR and ribosome. These findings provide a framework for understanding the physiological regulation of MTLR and guiding drug design targeting MTLR for the treatment of GI motility disorders. Structural basis for motilin and erythromycin recognition by motilin receptor.,You C, Zhang Y, Xu Y, Xu P, Li Z, Li H, Huang S, Chen Z, Li J, Xu HE, Jiang Y Sci Adv. 2023 Mar 17;9(11):eade9020. doi: 10.1126/sciadv.ade9020. Epub 2023 Mar , 15. PMID:36921049[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Escherichia coli | Homo sapiens | Large Structures | Jiang Y | Xu HE | Xu Y | You C
