7DTY

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

Summary for 7DTY

• Entry DOI: 10.2210/pdb7dty/pdb
• EMDB information: 30860
• Descriptor: human glucose-dependent insulinotropic polypeptide receptor, Gastric inhibitory polypeptide, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (7 entities in total)
• Functional Keywords: glucose-dependent insulinotropic polypeptide receptor; cryo-electron microscopy; g protein-coupled receptor; ligand recognition, structural protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 181419.80

Authors

Zhao, F.H.,Zhang, C.,Zhou, Q.T.,Hang, K.N.,Zou, X.Y.,Chen, Y.,Wu, F.,Rao, Q.D.,Dai, A.T.,Yin, W.C.,Shen, D.D.,Zhang, Y.,Xia, T.,Stevens, R.C.,Xu, H.E.,Yang, D.H.,Zhao, L.H.,Wang, M.W. (deposition date: 2021-01-06, release date: 2021-08-04, Last modification date: 2024-10-16)

Primary citation

Zhao, F.,Zhang, C.,Zhou, Q.,Hang, K.,Zou, X.,Chen, Y.,Wu, F.,Rao, Q.,Dai, A.,Yin, W.,Shen, D.D.,Zhang, Y.,Xia, T.,Stevens, R.C.,Xu, H.E.,Yang, D.,Zhao, L.,Wang, M.W.
Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor.
Elife, 10:-, 2021

PubMed Abstract: 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.

PubMed: 34254582
DOI: 10.7554/eLife.68719

Experimental method

ELECTRON MICROSCOPY (2.98 Å)