7dty

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Structural basis of ligand selectivity conferred by the human glucose-dependent insulinotropic polypeptide receptor

Structural highlights

7dty is a 6 chain structure with sequence from Bos taurus, Homo sapiens, Rattus norvegicus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.98Å
Ligands:CLR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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(s) heterotrimer at a global resolution of 2.9 A. 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.

Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor.,Zhao F, Zhang C, Zhou Q, Hang K, Zou X, Chen Y, Wu F, Rao Q, Dai A, Yin W, Shen DD, Zhang Y, Xia T, Stevens RC, Xu HE, Yang D, Zhao L, Wang MW Elife. 2021 Jul 13;10:e68719. doi: 10.7554/eLife.68719. PMID:34254582[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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References

  1. Zhao F, Zhang C, Zhou Q, Hang K, Zou X, Chen Y, Wu F, Rao Q, Dai A, Yin W, Shen DD, Zhang Y, Xia T, Stevens RC, Xu HE, Yang D, Zhao L, Wang MW. Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor. Elife. 2021 Jul 13;10:e68719. PMID:34254582 doi:10.7554/eLife.68719

Contents


PDB ID 7dty

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