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Botulinum neurotoxi...
Botulinum neurotoxin D-C uses synaptotagmin I and II as receptors, and human synaptotagmin II is not an effective receptor for type B, D-C and G toxins
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Peng, Lisheng (författare)
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- Berntsson, Ronnie P. (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Tepp, William H. (författare)
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Pitkin, Rose M. (författare)
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Johnson, Eric A. (författare)
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- Stenmark, Pål (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Dong, Min (författare)
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(creator_code:org_t)
- 2012-01-01
- 2012
- Engelska.
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 125:13, s. 3233-3242
- Relaterad länk:
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https://jcs.biologis...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Botulinum neurotoxins (BoNTs) are classified into seven types (A-G), but multiple subtype and mosaic toxins exist. These subtype and mosaic toxins share a high sequence identity, and presumably the same receptors and substrates with their parental toxins. Here, we report that a mosaic toxin, type D-C (BoNT/D-C), uses different receptors from its parental toxin BoNT/C. BoNT/D-C, but not BoNT/C, binds directly to the luminal domains of synaptic vesicle proteins synaptotagmin (Syt) I and II, and requires expression of SytI/II to enter neurons. The SytII luminal fragment containing the toxin-binding site can block the entry of BoNT/D-C into neurons and reduce its toxicity in vivo in mice. We also found that gangliosides increase binding of BoNT/D-C to SytI/II and enhance the ability of the SytII luminal fragment to block BoNT/D-C entry into neurons. These data establish SytI/II, in conjunction with gangliosides, as the receptors for BoNT/D-C, and indicate that BoNT/D-C is functionally distinct from BoNT/C. We further found that BoNT/D-C recognizes the same binding site on SytI/II where BoNT/B and G also bind, but utilizes a receptor-binding interface that is distinct from BoNT/B and G. Finally, we also report that human and chimpanzee SytII has diminished binding and function as the receptor for BoNT/B, D-C and G owing to a single residue change from rodent SytII within the toxin binding site, potentially reducing the potency of these BoNTs in humans and chimpanzees.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Botulinum neurotoxin
- Botulinum neurotoxin B
- Botulinum toxin
- Botulism
- Synaptotagmin
- Biochemistry
- biokemi
- Cell Biology
- cellbiologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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