Botulinum neurotoxin type E

Details

Name
Botulinum neurotoxin type E
Kind
protein
Synonyms
  • 3.4.24.69
  • BoNT/E
  • Bontoxilysin-E
Gene Name
Not Available
UniProtKB Entry
Q00496Swiss-Prot
Organism
Clostridium botulinum
NCBI Taxonomy ID
1491
Amino acid sequence
>lcl|BSEQ0051613|Botulinum neurotoxin type E
MPKINSFNYNDPVNDRTILYIKPGGCQEFYKSFNIMKNIWIIPERNVIGTTPQDFHPPTS
LKNGDSSYYDPNYLQSDEEKDRFLKIVTKIFNRINNNLSGGILLEELSKANPYLGNDNTP
DNQFHIGDASAVEIKFSNGSQDILLPNVIIMGAEPDLFETNSSNISLRNNYMPSNHRFGS
IAIVTFSPEYSFRFNDNCMNEFIQDPALTLMHELIHSLHGLYGAKGITTKYTITQKQNPL
ITNIRGTNIEEFLTFGGTDLNIITSAQSNDIYTNLLADYKKIASKLSKVQVSNPLLNPYK
DVFEAKYGLDKDASGIYSVNINKFNDIFKKLYSFTEFDLRTKFQVKCRQTYIGQYKYFKL
SNLLNDSIYNISEGYNINNLKVNFRGQNANLNPRIITPITGRGLVKKIIRFCKNIVSVKG
IRKSICIEINNGELFFVASENSYNDDNINTPKEIDDTVTSNNNYENDLDQVILNFNSESA
PGLSDEKLNLTIQNDAYIPKYDSNGTSDIEQHDVNELNVFFYLDAQKVPEGENNVNLTSS
IDTALLEQPKIYTFFSSEFINNVNKPVQAALFVSWIQQVLVDFTTEANQKSTVDKIADIS
IVVPYIGLALNIGNEAQKGNFKDALELLGAGILLEFEPELLIPTILVFTIKSFLGSSDNK
NKVIKAINNALKERDEKWKEVYSFIVSNWMTKINTQFNKRKEQMYQALQNQVNAIKTIIE
SKYNSYTLEEKNELTNKYDIKQIENELNQKVSIAMNNIDRFLTESSISYLMKIINEVKIN
KLREYDENVKTYLLNYIIQHGSILGESQQELNSMVTDTLNNSIPFKLSSYTDDKILISYF
NKFFKRIKSSSVLNMRYKNDKYVDTSGYDSNININGDVYKYPTNKNQFGIYNDKLSEVNI
SQNDYIIYDNKYKNFSISFWVRIPNYDNKIVNVNNEYTIINCMRDNNSGWKVSLNHNEII
WTFEDNRGINQKLAFNYGNANGISDYINKWIFVTITNDRLGDSKLYINGNLIDQKSILNL
GNIHVSDNILFKIVNCSYTRYIGIRYFNIFDKELDETEIQTLYSNEPNTNILKDFWGNYL
LYDKEYYLLNVLKPNNFIDRRKDSTLSINNIRSTILLANRLYSGIKVKIQRVNNSSTNDN
LVRKNDQVYINFVASKTHLFPLYADTATTNKEKTIKISSSGNRFNQVVVMNSVGNCTMNF
KNNNGNNIGLLGFKADTVVASTWYYTHMRDHTNSNGCFWNFISEEHGWQEK
Number of residues
1251
Molecular Weight
143842.99
Theoretical pI
Not Available
GO Classification
Functions
metalloendopeptidase activity / protein transmembrane transporter activity / toxin activity / zinc ion binding
Processes
inhibition of neurotransmitter uptake
Components
extracellular region / host cell cytosol / host cell junction / host cell presynaptic membrane / integral component of membrane
General Function
Botulinum neurotoxin type E Botulinum toxin causes flaccid paralysis by inhibiting neurotransmitter (acetylcholine) release from the presynaptic membranes of nerve terminals of eukaryotic host skeletal and autonomic nervous system, with frequent heart or respiratory failure. Precursor of botulinum neurotoxin E which has 2 coreceptors; complex polysialylated gangliosides found on neural tissue and specific membrane-anchored proteins found in synaptic vesicles. Receptor proteins are exposed on host presynaptic cell membrane during neurotransmitter release, when the toxin heavy chain (HC) binds to them (PubMed:19476346, PubMed:19650874). 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 HC forms pores that allows the light chain (LC) to translocate into the cytosol (PubMed:22720883). 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). Electrical stimulation increases uptake of toxin, probably by transiently exposing a receptor found in eukaryotic target synaptic vesicles (PubMed:19476346, PubMed:19650874). Uses the large lumenal domain of synaptic vesicle glycoproteins 2A and 2B (SV2A and SV2B) but not SV2C as receptor; an N-linked glycan of SV2 is essential for receptor function (PubMed:18815274, PubMed:19476346). Host cell gangliosides are also required for neurotoxin uptake and full toxicity (PubMed:18815274, PubMed:19650874). BoNT/E is a 'coincidence detector'; it requires simultaneous binding to coreceptor GT1b and low pH to transform into a membrane-bound, oligomeric channel (PubMed:22720883). Requires trypsinization and reduction before it can be used in assays in vitro (PubMed:8294407).
Specific Function
lipid 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 IDQ00496
UniProtKB Entry NameBXE_CLOBO
PDB ID(s)1T3A, 1T3C, 1ZKW, 1ZKX, 1ZL5, 1ZL6, 1ZN3, 3FFZ
KEGG IDag:CAA43999
General References
  1. Poulet S, Hauser D, Quanz M, Niemann H, Popoff MR: Sequences of the botulinal neurotoxin E derived from Clostridium botulinum type E (strain Beluga) and Clostridium butyricum (strains ATCC 43181 and ATCC 43755). Biochem Biophys Res Commun. 1992 Feb 28;183(1):107-13. [Article]
  2. Whelan SM, Elmore MJ, Bodsworth NJ, Atkinson T, Minton NP: The complete amino acid sequence of the Clostridium botulinum type-E neurotoxin, derived by nucleotide-sequence analysis of the encoding gene. Eur J Biochem. 1992 Mar 1;204(2):657-67. [Article]
  3. Binz T, Kurazono H, Wille M, Frevert J, Wernars K, Niemann H: The complete sequence of botulinum neurotoxin type A and comparison with other clostridial neurotoxins. J Biol Chem. 1990 Jun 5;265(16):9153-8. [Article]
  4. Schmidt JJ, Sathyamoorthy V, DasGupta BR: Partial amino acid sequences of botulinum neurotoxins types B and E. Arch Biochem Biophys. 1985 May 1;238(2):544-8. [Article]
  5. Gimenez JA, DasGupta BR: Botulinum neurotoxin type E fragmented with endoproteinase Lys-C reveals the site trypsin nicks and homology with tetanus neurotoxin. Biochimie. 1990 Apr;72(4):213-7. [Article]
  6. Campbell KD, Collins MD, East AK: Gene probes for identification of the botulinal neurotoxin gene and specific identification of neurotoxin types B, E, and F. J Clin Microbiol. 1993 Sep;31(9):2255-62. [Article]
  7. Schiavo G, Santucci A, Dasgupta BR, Mehta PP, Jontes J, Benfenati F, Wilson MC, Montecucco C: Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds. FEBS Lett. 1993 Nov 29;335(1):99-103. [Article]
  8. Binz T, Blasi J, Yamasaki S, Baumeister A, Link E, Sudhof TC, Jahn R, Niemann H: Proteolysis of SNAP-25 by types E and A botulinal neurotoxins. J Biol Chem. 1994 Jan 21;269(3):1617-20. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Equine Botulinum Neurotoxin E Immune FAB2approved, experimental, investigationalyestargetantibodyDetails