4FZ1

Crystal structure of acid-sensing ion channel in complex with psalmotoxin 1 at high pH

4FZ1 の概要

• エントリーDOI: 10.2210/pdb4fz1/pdb
• 関連するPDBエントリー: 4FZ0
• 分子名称: Acid-sensing ion channel 1, Pi-theraphotoxin-Pc1a, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: inhibitor cystine knot, transport protein
• 由来する生物種: Gallus gallus (bantam,chickens); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56475.28

構造登録者

Baconguis, I.,Gouaux, E. (登録日: 2012-07-05, 公開日: 2012-08-01, 最終更新日: 2024-10-16)

主引用文献

Baconguis, I.,Gouaux, E.
Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes.
Nature, 489:400-405, 2012

PubMed Abstract: Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-selective and Na(+)-selective currents in chicken ASIC1a at pH 7.25 and 5.5, respectively. Crystal structures of ASIC1a-psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. At pH 7.25 the pore is approximately 10 Å in diameter, whereas at pH 5.5 the pore is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7 Å, consistent with a barrier mechanism for ion selectivity. These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents.

PubMed: 22842900
DOI: 10.1038/nature11375

実験手法

X-RAY DIFFRACTION (3.359 Å)