Molecular mechanisms of receptor recognition by Clostridium botulinum neurotoxins.
| Project/Area Number |
09660343
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
KOZAKI Shunji Osaka Prefecture University, Department of Agriculture.Associate Professor, 農学部, 助教授 (10109895)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Clostridium botulinum / neurotoxin / recptor / synaptotagmin / synaptobrevin / ganglioside / ボツリヌス毒素 / 神経毒 |
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| Research Abstract |
Clostridium botulinum type B neurotoxin recognizes a complex of synaptotagmin II and ganglioside GTlb/GD1a as the high-affinity binding site. Recombinant deletion mutant of synaptotagmin II allowed us to demonstrate that the N-terminal domain including the transmembrane region retain the toxin binding activity while the C-terminal domain is not involved in constituting the toxin receptor. The direct binding of GTlb to the deletion mutants revealed that the transmembrane region is required to bind GTlb, suggesting that synaptotagmin II bind to the ceramide portion of ganglioside within the plasma membrane. Monoclonal antibody against GTlb effectively inhibited not only type B neurotoxin but also type A neurotoxin binding to brain synaptosomes. In addition, the monoclonal antibody antagonized the action of both neurotoxins on synaptic transmisstion of rat superior cervival ganglion neurons. They suggest that GTlb functions as a component of the receptor complex.
The neurotoxin of the strain associated with type B infant botulism showed antigenic and biological properties different from that of food-borne botulism-related strain. The neurotoxin derived from infant botulism was found to possess a toxicity 10 times lower than that of the authentic neurotoxin. However, synaptobrevin, an intracellular target protein, was digested to the same extent by both neurotoxins. Therefore, we concluded that such low toxicity of infant botulism-related neurotoxin is attributed to the receptor-recognition site in the molecule.
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Report
(3 results)
Research Products
(14 results)
