EMD-30860
Structural basis of ligand selectivity conferred by the human glucose-dependent insulinotropic polypeptide receptor
EMD-30860
Single-particle2.98 Å
Deposition: 06/01/2021Map released: 04/08/2021
Last modified: 16/10/2024
Sample Organism:
Homo sapiens,
Bos taurus,
Rattus norvegicus,
synthetic construct
Sample: Cryo-EM structure of the human glucose-dependent insulinotropic polypeptide receptor in complex with GIP and G protein
Fitted models: 7dty (Avg. Q-score: 0.436)
Deposition Authors: Zhao FH, Zhang C, Zhou QT, Hang KN, Zou XY, Chen Y, Wu F, Rao QD, Dai AT, Yin WC, Shen DD, Zhang Y, Xia T, Stevens RC, Xu HE
,
Yang DH,
Zhao LH,
Wang MW
Sample: Cryo-EM structure of the human glucose-dependent insulinotropic polypeptide receptor in complex with GIP and G protein
Fitted models: 7dty (Avg. Q-score: 0.436)
Deposition Authors: Zhao FH, Zhang C, Zhou QT, Hang KN, Zou XY, Chen Y, Wu F, Rao QD, Dai AT, Yin WC, Shen DD, Zhang Y, Xia T, Stevens RC, Xu HE
,
Yang DH,
Zhao LH,
Wang MW
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
(2021) eLife , 10
,
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
(2021) eLife , 10
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 Gs 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.
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 Gs 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.