5XEZ

Structure of the Full-length glucagon class B G protein-coupled receptor

5XEZ の概要

• エントリーDOI: 10.2210/pdb5xez/pdb
• 関連するPDBエントリー: 5XF1
• 分子名称: Glucagon receptor,Endolysin,Glucagon receptor, Antibody, mAb1, heavy chain, Antibody, mAb1, light chain, ... (6 entities in total)
• 機能のキーワード: human gcgr receptor, class b, 7tm domain, membrane, lcp, xfel, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 231984.65

構造登録者

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.,Sierra, R.,Weierstall, U.,Nelson, G.,Liu, W.,Wu, Y.,Ma, L.,Cai, X.,Lin, G.,Wu, X.,Geng, Z.,Dong, Y.,Song, G.,Griffin, P.,Lau, J.,Cherezov, V.,Yang, H.,Hanson, M.,Stevens, R.,Jiang, H.,Wang, M.,Zhao, Q.,Wu, B. (登録日: 2017-04-06, 公開日: 2017-05-24, 最終更新日: 2024-11-13)

主引用文献

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.
Structure of the full-length glucagon class B G-protein-coupled receptor.
Nature, 546:259-264, 2017

PubMed Abstract: 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.

PubMed: 28514451
DOI: 10.1038/nature22363

実験手法

X-RAY DIFFRACTION (3 Å)