X-ray structure of a prokaryotic pentameric ligand-gated ion channel
X-ray structure of a prokaryotic pentameric ligand-gated ion channel
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DOI：
10.1038/nature06717
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发表时间：
2008-03-20
期刊：
影响因子：
64.8
通讯作者：
Dutzler, Raimund
中科院分区：
文献类型：
--
作者：
Hilf, Ricarda J. C.;Dutzler, Raimund
五聚体配体门控离子通道（pLGIC）是化学突触早期电信号转导的关键参与者。该家族编码结构保守的通道蛋白支架，其响应于神经递质分子的结合而打开。所有蛋白质都具有相同或相关亚基的五聚体结构，其由细胞外配体结合结构域和随后的跨膜通道结构域组成。烟碱乙酰胆碱受体（nAChR）是pLGIC家族中研究最彻底的成员（最近的综述见参考文献1 - 3）。结构信息的两个来源为家庭提供了建筑框架。可溶性乙酰胆碱结合蛋白（AChBP）的结构定义了细胞外结构域的组织，并揭示了配体相互作用的化学基础（4-6）。电子显微镜研究来自电鳐电射线的nAChR已经产生了全长蛋白质的图片，并且最近导致了4.0埃分辨率的电子密度图的解释（7-9）。尽管有丰富的实验信息，但迄今为止还没有任何家族成员的高分辨率结构。直到最近，pLGIC被认为仅在多细胞真核生物中表达。然而，原核生物基因组序列的丰富性允许在细菌来源中鉴定几种同源蛋白质（10，11）。在这里，我们提出了在3.3埃分辨率的原核pLGIC从细菌欧文氏菌（ELIC）的X射线结构。我们的研究揭示了高分辨率的pLGIC的第一个结构，并提供了一个重要的模型系统的调查的一般机制的离子渗透和门控家庭。
Pentameric ligand- gated ion channels ( pLGICs) are key players in the early events of electrical signal transduction at chemical synapses. The family codes for a structurally conserved scaffold of channel proteins that open in response to the binding of neurotransmitter molecules. All proteins share a pentameric organization of identical or related subunits that consist of an extracellular ligand- binding domain followed by a transmembrane channel domain. The nicotinic acetylcholine receptor ( nAChR) is the most thoroughly studied member of the pLGIC family ( for recent reviews see refs 1 - 3). Two sources of structural information provided an architectural framework for the family. The structure of the soluble acetylcholine- binding protein ( AChBP) defined the organization of the extracellular domain and revealed the chemical basis of ligand interaction(4-6). Electron microscopy studies of the nAChR from Torpedo electric ray have yielded a picture of the full- length protein and have recently led to the interpretation of an electron density map at 4.0 angstrom resolution(7-9). Despite the wealth of experimental information, high- resolution structures of any family member have so far not been available. Until recently, the pLGICs were believed to be only expressed in multicellular eukaryotic organisms. The abundance of prokaryotic genome sequences, however, allowed the identification of several homologous proteins in bacterial sources(10,11). Here we present the X- ray structure of a prokaryotic pLGIC from the bacterium Erwinia chrysanthemi ( ELIC) at 3.3 angstrom resolution. Our study reveals the first structure of a pLGIC at high resolution and provides an important model system for the investigation of the general mechanisms of ion permeation and gating within the family.