9B95

Cryo-EM structure of the closed NF449-bound human P2X1 receptor

これはPDB形式変換不可エントリーです。

9B95 の概要

• エントリーDOI: 10.2210/pdb9b95/pdb
• 関連するPDBエントリー: 9B73
• EMDBエントリー: 44370
• 分子名称: P2X purinoceptor 1, 4,4',4'',4'''-{carbonylbis[azanediylbenzene-5,1,3-triylbis(carbonylazanediyl)]}tetra(benzene-1,3-disulfonic acid), 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: ion channel, trimer, nf449-bound, closed., membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 139768.20

構造登録者

Felix, M.B.,Alisa, G.,Hariprasad, V.,Jesse, I.M.,David, M.T. (登録日: 2024-04-01, 公開日: 2024-10-09, 最終更新日: 2024-10-30)

主引用文献

Bennetts, F.M.,Venugopal, H.,Glukhova, A.,Mobbs, J.I.,Ventura, S.,Thal, D.M.
Structural insights into the human P2X1 receptor and ligand interactions.
Nat Commun, 15:8418-8418, 2024

PubMed Abstract: The P2X1 receptor is a trimeric ligand-gated ion channel that plays an important role in urogenital and immune functions, offering the potential for new drug treatments. However, progress in this area has been hindered by limited structural information and a lack of well-characterised tool compounds. In this study, we employ cryogenic electron microscopy (cryo-EM) to elucidate the structures of the P2X1 receptor in an ATP-bound desensitised state and an NF449-bound closed state. NF449, a potent P2X1 receptor antagonist, engages the receptor distinctively, while ATP, the endogenous ligand, binds in a manner consistent with other P2X receptors. To explore the molecular basis of receptor inhibition, activation, and ligand interactions, key residues involved in ligand and metal ion binding were mutated. Radioligand binding assays with [H]-α,β-methylene ATP and intracellular calcium ion influx assays were used to evaluate the effects of these mutations. These experiments validate key ligand-receptor interactions and identify conserved and non-conserved residues critical for ligand binding or receptor modulation. This research expands our understanding of the P2X1 receptor structure at a molecular level and opens new avenues for in silico drug design targeting the P2X1 receptor.

PubMed: 39341830
DOI: 10.1038/s41467-024-52776-7

実験手法

ELECTRON MICROSCOPY (2.61 Å)