7DTY

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

7DTY の概要

• エントリーDOI: 10.2210/pdb7dty/pdb
• EMDBエントリー: 30860
• 分子名称: human glucose-dependent insulinotropic polypeptide receptor, Gastric inhibitory polypeptide, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (7 entities in total)
• 機能のキーワード: glucose-dependent insulinotropic polypeptide receptor; cryo-electron microscopy; g protein-coupled receptor; ligand recognition, structural protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 181419.80

構造登録者

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. (登録日: 2021-01-06, 公開日: 2021-08-04, 最終更新日: 2025-06-25)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.98 Å)