6W2Y

CryoEM Structure of GABAB1b Homodimer

6W2Y の概要

• エントリーDOI: 10.2210/pdb6w2y/pdb
• EMDBエントリー: 21533 21534
• 分子名称: Gamma-aminobutyric acid type B receptor subunit 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: inhibitor, homodimer, gpcr, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 192425.99

構造登録者

Papasergi-Scott, M.M.,Robertson, M.J.,Skiniotis, G. (登録日: 2020-03-08, 公開日: 2020-07-01, 最終更新日: 2024-10-30)

主引用文献

Papasergi-Scott, M.M.,Robertson, M.J.,Seven, A.B.,Panova, O.,Mathiesen, J.M.,Skiniotis, G.
Structures of metabotropic GABABreceptor.
Nature, 584:310-314, 2020

PubMed Abstract: Stimulation of the metabotropic GABA receptor by γ-aminobutyric acid (GABA) results in prolonged inhibition of neurotransmission, which is central to brain physiology. GABA belongs to family C of the G-protein-coupled receptors, which operate as dimers to transform synaptic neurotransmitter signals into a cellular response through the binding and activation of heterotrimeric G proteins. However, GABA is unique in its function as an obligate heterodimer in which agonist binding and G-protein activation take place on distinct subunits. Here we present cryo-electron microscopy structures of heterodimeric and homodimeric full-length GABA receptors. Complemented by cellular signalling assays and atomistic simulations, these structures reveal that extracellular loop 2 (ECL2) of GABA has an essential role in relaying structural transitions by ordering the linker that connects the extracellular ligand-binding domain to the transmembrane region. Furthermore, the ECL2 of each of the subunits of GABA caps and interacts with the hydrophilic head of a phospholipid that occupies the extracellular half of the transmembrane domain, thereby providing a potentially crucial link between ligand binding and the receptor core that engages G proteins. These results provide a starting framework through which to decipher the mechanistic modes of signal transduction mediated by GABA dimers, and have important implications for rational drug design that targets these receptors.

PubMed: 32580208
DOI: 10.1038/s41586-020-2469-4

実験手法

ELECTRON MICROSCOPY (3.2 Å)