Receptor and substrate interactions of clostridial neurotoxins

被引：71

作者：

Brunger, Axel T. ^{[1
,2
,3
,4
,5
]}

Rummel, Andreas ^{[6
]}

机构：

[1] Stanford Univ, JH Clark Ctr, Howard Hughes Med Inst, Stanford, CA 94305 USA

[2] Stanford Univ, JH Clark Ctr, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA

[3] Stanford Univ, JH Clark Ctr, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

[4] Stanford Univ, JH Clark Ctr, Dept Biol Struct, Stanford, CA 94305 USA

[5] Stanford Univ, JH Clark Ctr, Dept Photon Sci, Stanford, CA 94305 USA

[6] Hannover Med Sch, Inst Toxikol, D-30623 Hannover, Germany

来源：

TOXICON | 2009年 / 54卷 / 05期

关键词：

Protease; SNARE; Synaptic vesicle; Neurotransmission; Synaptotagmin; Ganglioside; Botulinum neurotoxin; BOTULINUM TYPE-B; TETANUS TOXIN REQUIRES; LIGHT-CHAIN PROTEASE; H-C FRAGMENT; CRYSTAL-STRUCTURE; SYNAPTOTAGMIN-II; BINDING-SITE; STRUCTURAL-ANALYSIS; HIGH-AFFINITY; HEAVY-CHAIN;

D O I：

10.1016/j.toxicon.2008.12.027

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The high potency of clostridial neurotoxins relies predominantly on their neurospecific binding and specific hydrolysis of SNARE proteins. Their multi-step mode of mechanism can be ascribed to their multi-domain three-dimensional structure. The C-terminal H-cc-domain interacts subsequently with complex polysialo-gangliosides such as GT1b and a synaptic vesicle protein receptor via two neighbouring binding sites, resulting in highly specific uptake of the neurotoxins at synapses of cholinergic motoneurons. After its translocation the enzymatically active light chain specifically hydrolyses specific SNARE proteins, preventing SNARE complex assembly and thereby blocking exocytosis of neurotransmitter. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：550 / 560

页数：11

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