7XJL

Cryo-EM structure of the spexin-bound GALR2-miniGq complex

7XJL の概要

• エントリーDOI: 10.2210/pdb7xjl/pdb
• EMDBエントリー: 33231
• 分子名称: spexin, Guanine nucleotide-binding protein G(q) subunit alpha, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total)
• 機能のキーワード: gpcr, galanin receptor 2, minigq, spexin, signaling protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 144511.33

構造登録者

Jiang, W.,Zheng, S. (登録日: 2022-04-18, 公開日: 2022-06-29, 最終更新日: 2024-11-06)

主引用文献

Jiang, W.,Zheng, S.
Structural insights into galanin receptor signaling.
Proc.Natl.Acad.Sci.USA, 119:e2121465119-e2121465119, 2022

PubMed Abstract: Galanin is a biologically active neuropeptide, and functions through three distinct G protein–coupled receptors (GPCRs), namely GALR1, GALR2, and GALR3. GALR signaling plays important roles in regulating various physiological processes such as energy metabolism, neuropathic pain, epileptic activity, and sleep homeostasis. GALR1 and GALR3 signal through the Gi/o pathway, whereas GALR2 signals mainly through the Gq/11 pathway. However, the molecular basis for galanin recognition and G protein selectivity of GALRs remains poorly understood. Here, we report the cryoelectron microscopy structures of the GALR1-Go and the GALR2-Gq complexes bound to the endogenous ligand galanin or spexin. The galanin peptide mainly adopts an alpha helical structure, which binds at the extracellular vestibule of the receptors, nearly parallel to the membrane plane without penetrating deeply into the receptor core. Structural analysis combined with functional studies reveals important structural determinants for the G protein selectivity of GALRs as well as other class A GPCRs. In addition, we show that the zinc ion is a negative allosteric regulator of GALR1 but not GALR2. Our studies provide insight into the mechanisms of G protein selectivity of GPCRs and highlight a potential function of the neuromodulator zinc ion as a modulator of GPCR signaling in the central nervous system.

PubMed: 35594396
DOI: 10.1073/pnas.2121465119

実験手法

ELECTRON MICROSCOPY (3.5 Å)