梭菌神经毒素的受体与底物相互作用
Receptor and substrate interactions of clostridial neurotoxins.
作者信息
Brunger Axel T, Rummel Andreas
机构信息
The Howard Hughes Medical Institute and Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Structural Biology, and Photon Science, Stanford University, J.H. Clark Center, E300C, 318 Campus Drive, Stanford, CA 94305, USA.
出版信息
Toxicon. 2009 Oct;54(5):550-60. doi: 10.1016/j.toxicon.2008.12.027. Epub 2009 Mar 4.
Abstract
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.
摘要
梭菌神经毒素的高效力主要依赖于其对神经特异性的结合以及对SNARE蛋白的特异性水解。其多步骤作用机制可归因于其多结构域三维结构。C末端H(CC)结构域随后通过两个相邻的结合位点与复杂的多唾液酸神经节苷脂（如GT1b）和一种突触囊泡蛋白受体相互作用，导致神经毒素在胆碱能运动神经元突触处高度特异性摄取。在其转运后，具有酶活性的轻链特异性水解特定的SNARE蛋白，阻止SNARE复合物组装，从而阻断神经递质的胞吐作用。
相似文献
1
Receptor and substrate interactions of clostridial neurotoxins.
Toxicon. 2009 Oct;54(5):550-60. doi: 10.1016/j.toxicon.2008.12.027. Epub 2009 Mar 4.
2
Cell entry strategy of clostridial neurotoxins.
J Neurochem. 2009 Jun;109(6):1584-95. doi: 10.1111/j.1471-4159.2009.06093.x. Epub 2009 Apr 28.
3
Structural determinants of the specificity for synaptic vesicle-associated membrane protein/synaptobrevin of tetanus and botulinum type B and G neurotoxins.
J Biol Chem. 1996 Aug 23;271(34):20353-8. doi: 10.1074/jbc.271.34.20353.
4
Internalization and mechanism of action of clostridial toxins in neurons.
Neurotoxicology. 2005 Oct;26(5):761-7. doi: 10.1016/j.neuro.2004.12.012. Epub 2005 May 31.
5
Unique ganglioside recognition strategies for clostridial neurotoxins.
J Biol Chem. 2011 Sep 30;286(39):34015-22. doi: 10.1074/jbc.M111.272054. Epub 2011 Aug 17.
6
Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin.
Nature. 1992 Oct 29;359(6398):832-5. doi: 10.1038/359832a0.
7
Central effects of tetanus and botulinum neurotoxins.
Toxicon. 2009 Oct;54(5):593-9. doi: 10.1016/j.toxicon.2008.12.026. Epub 2009 Mar 3.
8
Double receptor anchorage of botulinum neurotoxins accounts for their exquisite neurospecificity.
Curr Top Microbiol Immunol. 2013;364:61-90. doi: 10.1007/978-3-642-33570-9_4.
9
[Molecular mechanism of action of tetanus toxin and botulinum neurotoxins].
Pathol Biol (Paris). 1994 Feb;42(2):173-82.
10
Functional characterisation of tetanus and botulinum neurotoxins binding domains.
J Cell Sci. 1999 Aug;112 ( Pt 16):2715-24. doi: 10.1242/jcs.112.16.2715.
引用本文的文献
1
Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update.
Arch Toxicol. 2022 Jun;96(6):1521-1539. doi: 10.1007/s00204-022-03271-9. Epub 2022 Mar 25.
2
Interaction between a Novel Oligopeptide Fragment of the Human Neurotrophin Receptor TrkB Ectodomain D5 and the C-Terminal Fragment of Tetanus Neurotoxin.
Molecules. 2021 Jun 30;26(13):3988. doi: 10.3390/molecules26133988.
3
Botulinum Toxin: From Poison to Possible Treatment for Spasticity in Spinal Cord Injury.
Int J Mol Sci. 2021 May 5;22(9):4886. doi: 10.3390/ijms22094886.
4
Botulinum Neurotoxins: Mechanism of Action.
Handb Exp Pharmacol. 2021;263:35-47. doi: 10.1007/164_2020_355.
5
Optimization of SNAP-25 and VAMP-2 Cleavage by Botulinum Neurotoxin Serotypes A-F Employing Taguchi Design-of-Experiments.
Toxins (Basel). 2019 Oct 11;11(10):588. doi: 10.3390/toxins11100588.
6
Botulinum neurotoxins A, B, C, E, and F preferentially enter cultured human motor neurons compared to other cultured human neuronal populations.
FEBS Lett. 2019 Sep;593(18):2675-2685. doi: 10.1002/1873-3468.13508. Epub 2019 Jul 4.
7
Functional detection of botulinum neurotoxin serotypes A to F by monoclonal neoepitope-specific antibodies and suspension array technology.
Sci Rep. 2019 Apr 2;9(1):5531. doi: 10.1038/s41598-019-41722-z.
8
Why Are Botulinum Neurotoxin-Producing Bacteria So Diverse and Botulinum Neurotoxins So Toxic?
Toxins (Basel). 2019 Jan 11;11(1):34. doi: 10.3390/toxins11010034.
9
Variations in the Botulinum Neurotoxin Binding Domain and the Potential for Novel Therapeutics.
Toxins (Basel). 2018 Oct 20;10(10):421. doi: 10.3390/toxins10100421.
10
Light Chain Diversity among the Botulinum Neurotoxins.
Toxins (Basel). 2018 Jul 2;10(7):268. doi: 10.3390/toxins10070268.
本文引用的文献
1
A potent peptidomimetic inhibitor of botulinum neurotoxin serotype A has a very different conformation than SNAP-25 substrate.
Structure. 2008 Oct 8;16(10):1588-97. doi: 10.1016/j.str.2008.07.011.
2
Substrate binding mode and its implication on drug design for botulinum neurotoxin A.
PLoS Pathog. 2008 Sep 26;4(9):e1000165. doi: 10.1371/journal.ppat.1000165.
3
Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E into neurons.
Mol Biol Cell. 2008 Dec;19(12):5226-37. doi: 10.1091/mbc.e08-07-0765. Epub 2008 Sep 24.
4
Crystal structure of botulinum neurotoxin type A in complex with the cell surface co-receptor GT1b-insight into the toxin-neuron interaction.
PLoS Pathog. 2008 Aug 15;4(8):e1000129. doi: 10.1371/journal.ppat.1000129.
5
Membrane Interaction of botulinum neurotoxin A translocation (T) domain. The belt region is a regulatory loop for membrane interaction.
J Biol Chem. 2008 Oct 10;283(41):27668-27676. doi: 10.1074/jbc.M802557200. Epub 2008 Aug 7.
6
Molecular basis for tetanus toxin coreceptor interactions.
Biochemistry. 2008 Jul 8;47(27):7179-86. doi: 10.1021/bi800640y. Epub 2008 Jun 11.
7
Substrate recognition mechanism of VAMP/synaptobrevin-cleaving clostridial neurotoxins.
J Biol Chem. 2008 Jul 25;283(30):21145-52. doi: 10.1074/jbc.M800610200. Epub 2008 May 29.
8
Catalytic features of the botulinum neurotoxin A light chain revealed by high resolution structure of an inhibitory peptide complex.
Biochemistry. 2008 May 27;47(21):5736-45. doi: 10.1021/bi8001067. Epub 2008 May 6.
9
Structure- and substrate-based inhibitor design for Clostridium botulinum neurotoxin serotype A.
J Biol Chem. 2008 Jul 4;283(27):18883-91. doi: 10.1074/jbc.M801240200. Epub 2008 Apr 22.
10
Identification of the receptor-binding sites in the carboxyl-terminal half of the heavy chain of botulinum neurotoxin types C and D.
Microb Pathog. 2008 Jun;44(6):484-93. doi: 10.1016/j.micpath.2007.12.003. Epub 2008 Jan 31.
Zotero 插件