Protein: Botulinum neurotoxin type D (BoNT/D) (Bontoxilysin-D) [Cleaved into: Botulinum neurotoxin D light chain (LC) (EC 3.4.24.69); Botulinum neurotoxin D heavy chain (HC)] (P19321)
Organism: Clostridium botulinum D phage (Clostridium botulinum D bacteriophage)
Function: Botulinum toxin causes flaccid paralysis by inhibiting neurotransmitter (acetylcholine) release from the presynaptic membranes of nerve terminals of the eukaryotic host skeletal and autonomic nervous system, with frequent heart or respiratory failure. Precursor of botulinum neurotoxin D for which a proteinaceous coreceptor is controversial. In double SV2A/SV2B knockout mice this toxin does not degrade its synaptobrevin target; introducing SV2A, SV2B or SV2C restores target cleavage. Recognition of SV2 by this toxin does not occur via SV2 glycosylation or its large extracellular loop 4. Another group does not find a convincing interaction with SV2. Thus a protein receptor for this BoNT serotype has yet to be definitively proven. Recognizes at least 1 complex polysialylated ganglioside found on neural tissue. Electrical stimulation increases uptake of toxin in an ex vivo assay, presumably by transiently exposing a receptor usually found in eukaryotic target synaptic vesicles. Upon synaptic vesicle recycling the toxin is taken up via the endocytic pathway; when the pH of the toxin-containing endosome drops a structural rearrangement occurs so that the N-terminus of the heavy chain (HC) forms pores that allows the light chain (LC) to translocate into the cytosol (By similarity). Once in the cytosol the disulfide bond linking the 2 subunits is reduced and LC cleaves its target protein on synaptic vesicles, preventing their fusion with the cytoplasmic membrane and thus neurotransmitter release (By similarity). Requires complex eukaryotic host polysialogangliosides for full neurotoxicity and for binding to neurons.
Subcellular location: [Botulinum neurotoxin type D]: Secreted {ECO:0000269|PubMed:11713244, ECO:0000269|PubMed:17581814, ECO:0000269|PubMed:2668193}.; SUBCELLULAR LOCATION: [Botulinum neurotoxin D light chain]: Secreted {ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:8569530}. Note=In animals that have ingested BoNT/D LC acts in the eukaryotic host cytosol (Probable). {ECO:0000305|PubMed:15584922, ECO:0000305|PubMed:8175689}.; SUBCELLULAR LOCATION: [Botulinum neurotoxin D heavy chain]: Secreted {ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:8569530}. Note=Upon incubation with hippocampal cell colocalizes with SV2C, probably in host synaptic vesicles (PubMed:21483489). Upon incubation with primary neurons HC colocalizes with synaptophysin probably in synaptic vesicles of presynaptic cells; a small portion also colocalizes with RAB5 and may be in synaptic vesicle protein sorting endosomes (PubMed:21632541). Probably integrates into the eukaryotic host synaptic vesicle membrane. {ECO:0000269|PubMed:21483489, ECO:0000269|PubMed:21632541, ECO:0000305}.
Interaction partners:
Sequence:
MTWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCLRLTKNSRDDSTCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNSINDSKILSLQNKKNALVDTSGYNAEVRVGDNVQLNTIYTNDFKLSSSGDKIIVNLNNNILYSAIYENSSVSFWIKISKDLTNSHNEYTIINSIEQNSGWKLCIRNGNIEWILQDVNRKYKSLIFDYSESLSHTGYTNKWFFVTITNNIMGYMKLYINGELKQSQKIEDLDEVKLDKTIVFGIDENIDENQMLWIRDFNIFSKELSNEDINIVYEGQILRNVIKDYWGNPLKFDTEYYIINDNYIDRYIAPESNVLVLVQYPDRSKLYTGNPITIKSVSDKNPYSRILNGDNIILHMLYNSRKYMIIRDTDTIYATQGGECSQNCVYALKLQSNLGNYGIGIFSIKNIVSKNKYCSQIFSSFRENTMLLADIYKPWRFSFKNAYTPVAVTNYETKLLSTSSFWKFISRDPGWVE