破伤风毒素的结构揭示了pH介导的结构域动态变化。
The structure of the tetanus toxin reveals pH-mediated domain dynamics.
作者信息
Masuyer Geoffrey, Conrad Julian, Stenmark Pål
机构信息
Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Science for Life Laboratory, Stockholm University, Solna, Sweden.
出版信息
EMBO Rep. 2017 Aug;18(8):1306-1317. doi: 10.15252/embr.201744198. Epub 2017 Jun 23.
Abstract
The tetanus neurotoxin (TeNT) is a highly potent toxin produced by that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a "closed" domain arrangement stabilised by two disulphide bridges, and the molecular details of the toxin's interaction with its polysaccharide receptor. An integrative analysis combining X-ray crystallography, solution scattering and single particle electron cryo-microscopy reveals pH-mediated domain rearrangements that may give TeNT the ability to adapt to the multiple environments encountered during intoxication, and facilitate binding to distinct receptors.
摘要
破伤风神经毒素（TeNT）是由[具体产生源未提及]产生的一种剧毒毒素，它抑制抑制性中间神经元的神经传递，在破伤风疾病中导致痉挛性麻痹。TeNT与其他梭菌神经毒素的不同之处在于其通过逆行轴突运输靶向中枢神经系统的独特能力。破伤风毒素的晶体结构显示出由两个二硫键稳定的“封闭”结构域排列，以及毒素与其多糖受体相互作用的分子细节。结合X射线晶体学、溶液散射和单颗粒电子冷冻显微镜的综合分析揭示了pH介导的结构域重排，这可能赋予TeNT适应中毒过程中遇到的多种环境并促进与不同受体结合的能力。
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