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Structure paper

タイトル	Phase-plate cryo-EM structure of a class B GPCR-G-protein complex.
ジャーナル・号・ページ	Nature, Vol. 546, Issue 7656, Page 118-123, Year 2017
掲載日	2017年6月1日
著者	Yi-Lynn Liang / Maryam Khoshouei / Mazdak Radjainia / Yan Zhang / Alisa Glukhova / Jeffrey Tarrasch / David M Thal / Sebastian G B Furness / George Christopoulos / Thomas Coudrat / Radostin Danev / Wolfgang Baumeister / Laurence J Miller / Arthur Christopoulos / Brian K Kobilka / Denise Wootten / Georgios Skiniotis / Patrick M Sexton /
PubMed 要旨	Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the structure of a full-length class B ...Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the structure of a full-length class B receptor, the calcitonin receptor, in complex with peptide ligand and heterotrimeric Gαβγ protein determined by Volta phase-plate single-particle cryo-electron microscopy. The peptide agonist engages the receptor by binding to an extended hydrophobic pocket facilitated by the large outward movement of the extracellular ends of transmembrane helices 6 and 7. This conformation is accompanied by a 60° kink in helix 6 and a large outward movement of the intracellular end of this helix, opening the bundle to accommodate interactions with the α5-helix of Gα. Also observed is an extended intracellular helix 8 that contributes to both receptor stability and functional G-protein coupling via an interaction with the Gβ subunit. This structure provides a new framework for understanding G-protein-coupled receptor function.
リンク	Nature / PubMed:28437792 / PubMed Central
手法	EM (単粒子)
解像度	4.1 Å
構造データ	8623 5uz7 EMDB-8623, PDB-5uz7: Volta phase plate cryo-electron microscopy structure of a calcitonin receptor-heterotrimeric Gs protein complex 手法: EM (単粒子) / 解像度: 4.1 Å
由来	homo sapiens (ヒト) lama glama (ラマ)
キーワード	SIGNALING PROTEIN / Class B G protein-coupled receptor Agonist-Receptor-G protein ternary complex Calcitonin receptor Active-state G protein-coupled receptor