| http://purl.uniprot.org/citations/19650874 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19650874 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19650874 | http://www.w3.org/2000/01/rdf-schema#comment | "The high toxicity of clostridial neurotoxins primarily results from their specific binding and uptake into neurons. At motor neurons, the seven botulinum neurotoxin serotypes A-G (BoNT/A-G) inhibit acetylcholine release, leading to flaccid paralysis, while tetanus neurotoxin blocks neurotransmitter release in inhibitory neurons, resulting in spastic paralysis. Uptake of BoNT/A, B, E and G requires a dual interaction with gangliosides and the synaptic vesicle (SV) proteins synaptotagmin or SV2, whereas little is known about the entry mechanisms of the remaining serotypes. Here, we demonstrate that BoNT/F as wells depends on the presence of gangliosides, by employing phrenic nerve hemidiaphragm preparations derived from mice expressing GM3, GM2, GM1 and GD1a or only GM3. Subsequent site-directed mutagenesis based on homology models identified the ganglioside binding site at a conserved location in BoNT/E and F. Using the mice phrenic nerve hemidiaphragm assay as a physiological model system, cross-competition of full-length neurotoxin binding by recombinant binding fragments, plus accelerated neurotoxin uptake upon increased electrical stimulation, indicate that BoNT/F employs SV2 as protein receptor, whereas BoNT/C and D utilise different SV receptor structures. The co-precipitation of SV2A, B and C from Triton-solubilised SVs by BoNT/F underlines this conclusion."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.org/dc/terms/identifier | "doi:10.1111/j.1471-4159.2009.06298.x"xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.org/dc/terms/identifier | "doi:10.1111/j.1471-4159.2009.06298.x"xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Beermann S."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Beermann S."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Bigalke H."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Bigalke H."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Binz T."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Binz T."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Darashchonak N."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Darashchonak N."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Haefner K."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Haefner K."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Holt M."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Holt M."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Jahn R."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Jahn R."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Karnath T."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Karnath T."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Mahrhold S."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Mahrhold S."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Rummel A."xsd:string |
| http://purl.uniprot.org/citations/19650874 | http://purl.uniprot.org/core/author | "Rummel A."xsd:string |