6AH4

Structure of human P2X3 receptor in complex with ATP and Ca2+ ion

6AH4 の概要

• エントリーDOI: 10.2210/pdb6ah4/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: P2X purinoceptor 3, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: channel, 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: 128030.36

構造登録者

Hattori, M. (登録日: 2018-08-16, 公開日: 2019-06-12, 最終更新日: 2024-11-06)

主引用文献

Li, M.,Wang, Y.,Banerjee, R.,Marinelli, F.,Silberberg, S.,Faraldo-Gomez, J.D.,Hattori, M.,Swartz, K.J.
Molecular mechanisms of human P2X3 receptor channel activation and modulation by divalent cation bound ATP.
Elife, 8:-, 2019

PubMed Abstract: P2X3 receptor channels expressed in sensory neurons are activated by extracellular ATP and serve important roles in nociception and sensory hypersensitization, making them attractive therapeutic targets. Although several P2X3 structures are known, it is unclear how physiologically abundant Ca-ATP and Mg-ATP activate the receptor, or how divalent cations regulate channel function. We used structural, computational and functional approaches to show that a crucial acidic chamber near the nucleotide-binding pocket in human P2X3 receptors accommodates divalent ions in two distinct modes in the absence and presence of nucleotide. The unusual engagement between the receptor, divalent ion and the γ-phosphate of ATP enables channel activation by ATP-divalent complex, cooperatively stabilizes the nucleotide on the receptor to slow ATP unbinding and recovery from desensitization, a key mechanism for limiting channel activity. These findings reveal how P2X3 receptors recognize and are activated by divalent-bound ATP, aiding future physiological investigations and drug development.

PubMed: 31232692
DOI: 10.7554/eLife.47060

実験手法

X-RAY DIFFRACTION (3.296 Å)