8TRJ

Cryo-EM structure of the rat P2X7 receptor in complex with the high-affinity agonist BzATP

これはPDB形式変換不可エントリーです。

8TRJ の概要

• エントリーDOI: 10.2210/pdb8trj/pdb
• 関連するPDBエントリー: 8TR5 8TR6 8TR7 8TR8 8TRA 8TRB 8TRK
• EMDBエントリー: 41570 41571 41572 41573 41575 41576 41581 41582
• 分子名称: P2X purinoceptor 7, 3'-O-(4-benzoylbenzoyl)adenosine 5'-(tetrahydrogen triphosphate), GUANOSINE-5'-DIPHOSPHATE, ... (7 entities in total)
• 機能のキーワード: membrane protein, ion channel, ligand-gate ion channel, p2x receptor, allosteric antagonist, high-affinity agonist
• 由来する生物種: Rattus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 215122.85

構造登録者

Oken, A.C.,Lisi, N.E.,Krishnamurthy, I.,McCarthy, A.E.,Godsey, M.H.,Glasfeld, A.,Mansoor, S.E. (登録日: 2023-08-09, 公開日: 2024-08-14, 最終更新日: 2025-05-14)

主引用文献

Oken, A.C.,Lisi, N.E.,Krishnamurthy, I.,McCarthy, A.E.,Godsey, M.H.,Glasfeld, A.,Mansoor, S.E.
High-affinity agonism at the P2X 7 receptor is mediated by three residues outside the orthosteric pocket.
Nat Commun, 15:6662-6662, 2024

PubMed Abstract: P2X receptors are trimeric ATP-gated ion channels that activate diverse signaling cascades. Due to its role in apoptotic pathways, selective activation of P2X is a potential experimental tool and therapeutic approach in cancer biology. However, mechanisms of high-affinity P2X activation have not been defined. We report high-resolution cryo-EM structures of wild-type rat P2X bound to the high-affinity agonist BzATP as well as significantly improved apo receptor structures in the presence and absence of sodium. Apo structures define molecular details of pore architecture and reveal how a partially hydrated Na ion interacts with the conductance pathway in the closed state. Structural, electrophysiological, and direct binding data of BzATP reveal that three residues just outside the orthosteric ATP-binding site are responsible for its high-affinity agonism. This work provides insights into high-affinity agonism for any P2X receptor and lays the groundwork for development of subtype-specific agonists applicable to cancer therapeutics.

PubMed: 39107314
DOI: 10.1038/s41467-024-50771-6

実験手法

ELECTRON MICROSCOPY (2.78 Å)