Botulinum neurotoxin type C1

Details

Name
Botulinum neurotoxin type C1
Synonyms
  • 3.4.24.69
  • BoNT/C1
  • Bontoxilysin-C1
Gene Name
Not Available
UniProtKB Entry
P18640Swiss-Prot
Organism
Clostridium botulinum
NCBI Taxonomy ID
1491
Amino acid sequence
>lcl|BSEQ0051611|Botulinum neurotoxin type C1
MPITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNK
PPRVTSPKSGYYDPNYLSTDSDKDPFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNN
NTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTF
AAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYG
IAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSI
AKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTE
FNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPA
LRKVNPENMLYLFTKFCHKAIDGRSLYNKTLDCRELLVKNTDLPFIGDISDVKTDIFLRK
DINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQN
VDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLM
WANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILL
EAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQF
NNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNIN
KFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSF
QNTIPFNIFSYTNNSLLKDIINEYFNNINDSKILSLQNRKNTLVDTSGYNAEVSEEGDVQ
LNPIFPFDFKLGSSGEDRGKVIVTQNENIVYNSMYESFSISFWIRINKWVSNLPGYTIID
SVKNNSGWSIGIISNFLVFTLKQNEDSEQSINFSYDISNNAPGYNKWFFVTVTNNMMGNM
KIYINGKLIDTIKVKELTGINFSKTITFEINKIPDTGLITSDSDNINMWIRDFYIFAKEL
DGKDINILFNSLQYTNVVKDYWGNDLRYNKEYYMVNIDYLNRYMYANSRQIVFNTRRNNN
DFNEGYKIIIKRIRGNTNDTRVRGGDILYFDMTINNKAYNLFMKNETMYADNHSTEDIYA
IGLREQTKDINDNIIFQIQPMNNTYYYASQIFKSNFNGENISGICSIGTYRFRLGGDWYR
HNYLVPTVKQGNYASLLESTSTHWGFVPVSE
Number of residues
1291
Molecular Weight
148864.57
Theoretical pI
Not Available
GO Classification
Functions
metalloendopeptidase activity / toxin activity / zinc ion binding
Processes
inhibition of neurotransmitter uptake / membrane protein proteolysis / negative regulation of calcium ion-dependent exocytosis
Components
extracellular region / host cell cytosol / host cell junction / host cell presynaptic membrane / integral component of membrane
General Function
Botulinum neurotoxin type C 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 (PubMed:16252491, PubMed:7901002, PubMed:8611567). Is unique among characterized BoNTs in having 2 substrates, syntaxin (STX) and SNAP25 (PubMed:17718519, PubMed:7737992, PubMed:7901002, PubMed:8611567, PubMed:9886085). Precursor of botulinum neurotoxin C which unlike most BoNTs seems not to have a proteinaceous coreceptor, and instead recognizes 2 different complex polysialylated gangliosides found on neural tissue probably found in synaptic vesicles (PubMed:21483489, PubMed:23027864). 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). In vitro the whole toxin only has protease activity after reduction (PubMed:8611567). Electrical stimulation increases uptake of toxin, presumably by transiently exposing a receptor usually found in eukaryotic target synaptic vesicles (PubMed:19650874). Forms ion-conducting channels at around pH 6.1 (PubMed:2424493). Requires complex eukaryotic host polysialogangliosides for full neurotoxicity (PubMed:19650874, PubMed:21483489). Synaptic vesicle glycoproteins (SV2) do not seem to act as its receptor (PubMed:21483489).
Specific Function
ganglioside binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
Not Available
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP18640
UniProtKB Entry NameBXC1_CLOBO
PDB ID(s)2QN0, 3DEB, 3N7K, 3R4S, 3R4U
General References
  1. Hauser D, Eklund MW, Kurazono H, Binz T, Niemann H, Gill DM, Boquet P, Popoff MR: Nucleotide sequence of Clostridium botulinum C1 neurotoxin. Nucleic Acids Res. 1990 Aug 25;18(16):4924. [Article]
  2. Kimura K, Fujii N, Tsuzuki K, Murakami T, Indoh T, Yokosawa N, Takeshi K, Syuto B, Oguma K: The complete nucleotide sequence of the gene coding for botulinum type C1 toxin in the C-ST phage genome. Biochem Biophys Res Commun. 1990 Sep 28;171(3):1304-11. [Article]
  3. Tsuzuki K, Yokosawa N, Syuto B, Ohishi I, Fujii N, Kimura K, Oguma K: Establishment of a monoclonal antibody recognizing an antigenic site common to Clostridium botulinum type B, C1, D, and E toxins and tetanus toxin. Infect Immun. 1988 Apr;56(4):898-902. [Article]
  4. Blasi J, Chapman ER, Yamasaki S, Binz T, Niemann H, Jahn R: Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin. EMBO J. 1993 Dec;12(12):4821-8. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Botulinum neurotoxin type C1 (Clostridium botulinum)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Equine Botulinum Neurotoxin C Immune FAB2approved, experimental, investigationalyestargetantibodyDetails