Structure of the full-length glucagon class B G-protein-coupled receptor
| Autor: | Venkatasubramanian Dharmarajan, Anna Qiao, Xiaoai Wu, Guangyao Lin, Raymond G. Sierra, Michael A. Hanson, Patrick R. Griffin, Gye Won Han, Thomas D. Grant, Hui Zhang, Yanhong Wu, Steffen Reedtz-Runge, Linlin Yang, Haonan Zhang, Dehua Yang, Ming-Wei Wang, Wei Liu, Hualiang Jiang, Huaiyu Yang, Garrett Nelson, Xiaoqing Cai, Yuhui Dong, Raymond C. Stevens, Beili Wu, Antao Dai, Vadim Cherezov, Zhi Geng, Uwe Weierstall, Gaojie Song, Chris de Graaf, Limin Ma, Qiang Zhao, Jesper Lau |
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| Přispěvatelé: | Medicinal chemistry, AIMMS |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Multidisciplinary Protein Conformation Protein domain Biology Ligands Article 3. Good health Receptors G-Protein-Coupled 03 medical and health sciences Transmembrane domain 030104 developmental biology 0302 clinical medicine Biochemistry Biophysics Glucose homeostasis Receptor Glucagon receptor Glucagon receptor family 030217 neurology & neurosurgery Glucagon-like peptide 1 receptor G protein-coupled receptor |
| Zdroj: | Zhang, H, Qiao, A, Yang, D, Yang, L, Dai, A, de Graaf, C, Reedtz-Runge, S, Dharmarajan, V, Zhang, H, Han, G W, Grant, T D, Sierra, R G, Weierstall, U, Nelson, G, Liu, W, Wu, Y, Ma, L, Cai, X, Lin, G, Wu, X, Geng, Z, Dong, Y, Song, G, Griffin, P R, Lau, J, Cherezov, V, Yang, H, Hanson, M A, Stevens, R C, Zhao, Q, Jiang, H, Wang, M W & Wu, B 2017, ' Structure of the full-length glucagon class B G-protein-coupled receptor ', Nature, vol. 546, no. 7657, pp. 259-264 . https://doi.org/10.1038/nature22363 Nature Nature, 546(7657), 259-264. Nature Publishing Group |
| ISSN: | 0028-0836 |
| Popis: | The human glucagon receptor, GCGR, belongs to the class B G-protein-coupled receptor family and plays a key role in glucose homeostasis and the pathophysiology of type 2 diabetes. Here we report the 3.0 Å crystal structure of full-length GCGR containing both the extracellular domain and transmembrane domain in an inactive conformation. The two domains are connected by a 12-residue segment termed the stalk, which adopts a β-strand conformation, instead of forming an α-helix as observed in the previously solved structure of the GCGR transmembrane domain. The first extracellular loop exhibits a β-hairpin conformation and interacts with the stalk to form a compact β-sheet structure. Hydrogen-deuterium exchange, disulfide crosslinking and molecular dynamics studies suggest that the stalk and the first extracellular loop have critical roles in modulating peptide ligand binding and receptor activation. These insights into the full-length GCGR structure deepen our understanding of the signalling mechanisms of class B G-protein-coupled receptors. |
| Databáze: | OpenAIRE |
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