EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Conformational plasticity of human acid-sensing ion channel 1a.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 33, Issue 8, Page 1171-1182, Year 2026
掲載日	2026年7月16日
著者	James Cahill / Kimberly A Hartfield / Stephanie Andrea Heusser / Nadine Ritter / Mette Homann Poulsen / Craig Yoshioka / Stephan Alexander Pless / Isabelle Baconguis /
PubMed 要旨	Acid-sensing ion channels (ASICs) are typically activated by acidic environments and contribute to nociception and synaptic plasticity. ASIC1a is the most abundant subunit in the central nervous ...Acid-sensing ion channels (ASICs) are typically activated by acidic environments and contribute to nociception and synaptic plasticity. ASIC1a is the most abundant subunit in the central nervous system and forms homomeric channels permeable to Na and Ca, making it a compelling therapeutic target for acidotic pathologies including stroke and traumatic brain injury. However, a complete conformational library of human ASIC1a has yet to be described. Here we show that human ASIC1a adopts six major conformations, resolved by cryo-electron microscopy across a pH range between 8.5 and 5.7 and in the presence of a toxin agonist and a gating-modifying amino acid substitution. These major conformations establish linear transmembrane helices to be associated with an open state, delineate mechanistic differences between proton and toxin activation and demonstrate that desensitization involves unexpected conformational diversity in the transmembrane domain. Together, they provide a three-dimensional framework to integrate previous structure-function studies on ASIC.
リンク	Nat Struct Mol Biol / PubMed:42463865 / PubMed Central
手法	EM (単粒子)
解像度	2.33 - 3.41 Å
構造データ	47503 9e4a EMDB-47503, PDB-9e4a: Human ASIC1a at pH 8.5 with domain-swapped transmembrane domain 手法: EM (単粒子) / 解像度: 2.74 Å 47504 9e4b EMDB-47504, PDB-9e4b: Human ASIC1a at pH 7.5 with domain-swapped transmembrane domain 手法: EM (単粒子) / 解像度: 3.09 Å 47505 9e4c EMDB-47505, PDB-9e4c: Human ASIC1a at pH 7.5 with partial transmembrane domain 手法: EM (単粒子) / 解像度: 3.41 Å 47506 9e4d EMDB-47506, PDB-9e4d: Human ASIC1a at pH 7.5 with linear transmembrane domain 手法: EM (単粒子) / 解像度: 3.19 Å 47507 9e4e EMDB-47507, PDB-9e4e: Human ASIC1a at pH 6.5 with linear transmembrane domain 手法: EM (単粒子) / 解像度: 3.16 Å 47508 9e4f EMDB-47508, PDB-9e4f: Human ASIC1a at pH 5.7 with domain-swapped transmembrane domain 手法: EM (単粒子) / 解像度: 2.69 Å 47509 9e4g EMDB-47509, PDB-9e4g: Human ASIC1a at pH 5.7 with linear transmembrane domain 手法: EM (単粒子) / 解像度: 2.8 Å 47510 9e4h EMDB-47510, PDB-9e4h: Human ASIC1a at pH 5.7 with rotated, domain-swapped transmembrane domain 手法: EM (単粒子) / 解像度: 2.61 Å 47511 9e4i EMDB-47511, PDB-9e4i: Human ASIC1a at pH 7.5 in complex with MitTx 手法: EM (単粒子) / 解像度: 2.33 Å 47512 9e4j EMDB-47512, PDB-9e4j: Human ASIC1a at pH 6.5 in complex with MitTx 手法: EM (単粒子) / 解像度: 2.87 Å 47513 9e4k EMDB-47513, PDB-9e4k: Human ASIC1a at pH 8.5, T26V mutation 手法: EM (単粒子) / 解像度: 2.77 Å
由来	homo sapiens (ヒト) micrurus tener tener (コブラ)
キーワード	MEMBRANE PROTEIN / Ion channel / Trimer / Toxin