6G79

Coupling specificity of heterotrimeric Go to the serotonin 5-HT1B receptor

6G79 の概要

• エントリーDOI: 10.2210/pdb6g79/pdb
• EMDBエントリー: 4358
• 分子名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Guanine nucleotide-binding protein G(o) subunit alpha, ... (5 entities in total)
• 機能のキーワード: g-protein coupled receptor, 5-ht1b, mini-go, serotonin, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 111964.40

構造登録者

Garcia-Nafria, J.,Nehme, R.,Edwards, P.,Tate, C.G. (登録日: 2018-04-05, 公開日: 2018-06-20, 最終更新日: 2024-11-13)

主引用文献

Garcia-Nafria, J.,Nehme, R.,Edwards, P.C.,Tate, C.G.
Cryo-EM structure of the serotonin 5-HT1Breceptor coupled to heterotrimeric Go.
Nature, 558:620-623, 2018

PubMed Abstract: G-protein-coupled receptors (GPCRs) form the largest family of receptors encoded by the human genome (around 800 genes). They transduce signals by coupling to a small number of heterotrimeric G proteins (16 genes encoding different α-subunits). Each human cell contains several GPCRs and G proteins. The structural determinants of coupling of G to four different GPCRs have been elucidated, but the molecular details of how the other G-protein classes couple to GPCRs are unknown. Here we present the cryo-electron microscopy structure of the serotonin 5-HT receptor (5-HTR) bound to the agonist donitriptan and coupled to an engineered G heterotrimer. In this complex, 5-HTR is in an active state; the intracellular domain of the receptor is in a similar conformation to that observed for the β-adrenoceptor (βAR) or the adenosine A receptor (AR) in complex with G. In contrast to the complexes with G, the gap between the receptor and the Gβ-subunit in the G-5-HTR complex precludes molecular contacts, and the interface between the Gα-subunit of G and the receptor is considerably smaller. These differences are likely to be caused by the differences in the interactions with the C terminus of the G α-subunit. The molecular variations between the interfaces of G and G in complex with GPCRs may contribute substantially to both the specificity of coupling and the kinetics of signalling.

PubMed: 29925951
DOI: 10.1038/s41586-018-0241-9

実験手法

ELECTRON MICROSCOPY (3.78 Å)