Nature：鸡ASIC1的高分辨率晶体结构

佚名

酸感应离子通道（ASIC）是质子激活的受体，它们存在于很多人体组织和器官中，在中枢和周围神经系统中尤其丰富。在小鼠实验中，研究人员发现它们与痛觉有关，也与条件性恐惧学习行为有关。它们是一个超级受体家族的成员，这个家族的受体参与从体内钠平衡到机械感觉在内的广泛的生物过程。不过此前，研究人员还不知道这一重要类别蛋白的结构。现在，来自Eric Gouaux实验室的一篇论文报告了在封闭状态下鸡ASIC1的高分辨率晶体结构。它是一个三聚体，与目前所研究过的任何其他通道都不同。它的大型细胞外部分（封面图片的上半部分，图上的横条代表细胞膜）多空腔和突起，含有一对涉及质子探测的酸性残基。

原始出处：
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: gouauxe@ohsu.edu).

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.