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TitleStructural basis for motilin and erythromycin recognition by motilin receptor.
Journal, issue, pagesSci Adv, Vol. 9, Issue 11, Page eade9020, Year 2023
Publish dateMar 17, 2023
AuthorsChongzhao You / Yumu Zhang / Youwei Xu / Peiyu Xu / Zhen Li / Huadong Li / Sijie Huang / Zecai Chen / Jingru Li / H Eric Xu / Yi Jiang /
PubMed AbstractMotilin 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), ...Motilin 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-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.
External linksSci Adv / PubMed:36921049 / PubMed Central
MethodsEM (single particle)
Resolution3.19 - 3.51 Å
Structure data

35345

8ibu

EMDB-35345, PDB-8ibu:
Cryo-EM structure of the erythromycin-bound motilin receptor-Gq protein complex
Method: EM (single particle) / Resolution: 3.51 Å

35346

8ibv

EMDB-35346, PDB-8ibv:
Cryo-EM structure of the motilin-bound motilin receptor-Gq protein complex
Method: EM (single particle) / Resolution: 3.19 Å

Chemicals

ChemComp-ERY:
ERYTHROMYCIN A / antibiotic*YM

Source
  • homo sapiens (human)
  • escherichia coli (E. coli)
KeywordsSIGNALING PROTEIN / Cryo-EM / GPCR / erythromycin / motilin receptor / Gq / complex / motilin

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