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TitleStructural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor.
Journal, issue, pagesElife, Vol. 10, Year 2021
Publish dateJul 13, 2021
AuthorsFenghui Zhao / Chao Zhang / Qingtong Zhou / Kaini Hang / Xinyu Zou / Yan Chen / Fan Wu / Qidi Rao / Antao Dai / Wanchao Yin / Dan-Dan Shen / Yan Zhang / Tian Xia / Raymond C Stevens / H Eric Xu / Dehua Yang / Lihua Zhao / Ming-Wei Wang /
PubMed AbstractGlucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that exerts crucial metabolic functions by binding and activating its cognate receptor, GIPR. As an important therapeutic ...Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that exerts crucial metabolic functions by binding and activating its cognate receptor, GIPR. As an important therapeutic target, GIPR has been subjected to intensive structural studies without success. Here, we report the cryo-EM structure of the human GIPR in complex with GIP and a G heterotrimer at a global resolution of 2.9 Å. GIP adopts a single straight helix with its N terminus dipped into the receptor transmembrane domain (TMD), while the C terminus is closely associated with the extracellular domain and extracellular loop 1. GIPR employs conserved residues in the lower half of the TMD pocket to recognize the common segments shared by GIP homologous peptides, while uses non-conserved residues in the upper half of the TMD pocket to interact with residues specific for GIP. These results provide a structural framework of hormone recognition and GIPR activation.
External linksElife / PubMed:34254582 / PubMed Central
MethodsEM (single particle)
Resolution2.98 Å
Structure data

30860

7dty

EMDB-30860, PDB-7dty:
Structural basis of ligand selectivity conferred by the human glucose-dependent insulinotropic polypeptide receptor
Method: EM (single particle) / Resolution: 2.98 Å

Chemicals

ChemComp-CLR:
CHOLESTEROL / Cholesterol

Source
  • homo sapiens (human)
  • bos taurus (cattle)
  • rattus norvegicus (Norway rat)
  • synthetic construct (others)
KeywordsSTRUCTURAL PROTEIN / Glucose-dependent insulinotropic polypeptide receptor; cryo-electron microscopy; G protein-coupled receptor; ligand recognition

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