酸感應(yīng)離子通道（ASIC）是質(zhì)子激活的受體,，它們存在于很多人體組織和器官中,，在中樞和周圍神經(jīng)系統(tǒng)中尤其豐富。在小鼠實驗中,，研究人員發(fā)現(xiàn)它們與痛覺有關(guān),，也與條件性恐懼學習行為有關(guān)。它們是一個超級受體家族的成員,，這個家族的受體參與從體內(nèi)鈉平衡到機械感覺在內(nèi)的廣泛的生物過程,。不過此前，研究人員還不知道這一重要類別蛋白的結(jié)構(gòu)?，F(xiàn)在,，來自Eric Gouaux實驗室的一篇論文報告了在封閉狀態(tài)下雞ASIC1的高分辨率晶體結(jié)構(gòu)。它是一個三聚體,，與目前所研究過的任何其他通道都不同,。它的大型細胞外部分（封面圖片的上半部分，圖上的橫條代表細胞膜）多空腔和突起,，含有一對涉及質(zhì)子探測的酸性殘基,。
原始出處：
Nature 449, 316-323 (20 September 2007) | doi:10.1038/nature06163; Received 4 June 2007; Accepted 10 August 2007
Structure of acid-sensing ion channel 1 at 1.9 Å resolution and low pH
Jayasankar Jasti1, Hiroyasu Furukawa1,3, Eric B. Gonzales1 & Eric Gouaux1,2
Vollum Institute and,
Howard Hughes Medical Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
Present address: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Correspondence to: Eric Gouaux1,2 Correspondence and requests for materials should be addressed to E.G. (Email: [email protected]).
Acid-sensing ion channels (ASICs) are voltage-independent, proton-activated receptors that belong to the epithelial sodium channel/degenerin family of ion channels and are implicated in perception of pain, ischaemic stroke, mechanosensation, learning and memory. Here we report the low-pH crystal structure of a chicken ASIC1 deletion mutant at 1.9 Å resolution. Each subunit of the chalice-shaped homotrimer is composed of short amino and carboxy termini, two transmembrane helices, a bound chloride ion and a disulphide-rich, multidomain extracellular region enriched in acidic residues and carboxyl-carboxylate pairs within 3 Å, suggesting that at least one carboxyl group bears a proton. Electrophysiological studies on aspartate-to-asparagine mutants confirm that these carboxyl-carboxylate pairs participate in proton sensing. Between the acidic residues and the transmembrane pore lies a disulphide-rich 'thumb' domain poised to couple the binding of protons to the opening of the ion channel, thus demonstrating that proton activation involves long-range conformational changes.
