Botulinum neurotoxin type D

Details

Name
Botulinum neurotoxin type D
Kind
protein
Synonyms
  • 3.4.24.69
  • BoNT/D
  • Bontoxilysin-D
Gene Name
botD
UniProtKB Entry
P19321Swiss-Prot
Organism
Clostridium botulinum
NCBI Taxonomy ID
1491
Amino acid sequence
>lcl|BSEQ0051612|Botulinum neurotoxin type D
MTWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSK
PPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDS
STPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSN
PSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYG
INIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDI
AKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSE
VVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPA
LQKLSSESVVDLFTKVCLRLTKNSRDDSTCIKVKNNRLPYVADKDSISQEIFENKIITDE
TNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYL
NSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANE
VVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFP
EFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHIN
YQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIR
ECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTM
PFNIFSYTNNSLLKDIINEYFNSINDSKILSLQNKKNALVDTSGYNAEVRVGDNVQLNTI
YTNDFKLSSSGDKIIVNLNNNILYSAIYENSSVSFWIKISKDLTNSHNEYTIINSIEQNS
GWKLCIRNGNIEWILQDVNRKYKSLIFDYSESLSHTGYTNKWFFVTITNNIMGYMKLYIN
GELKQSQKIEDLDEVKLDKTIVFGIDENIDENQMLWIRDFNIFSKELSNEDINIVYEGQI
LRNVIKDYWGNPLKFDTEYYIINDNYIDRYIAPESNVLVLVQYPDRSKLYTGNPITIKSV
SDKNPYSRILNGDNIILHMLYNSRKYMIIRDTDTIYATQGGECSQNCVYALKLQSNLGNY
GIGIFSIKNIVSKNKYCSQIFSSFRENTMLLADIYKPWRFSFKNAYTPVAVTNYETKLLS
TSSFWKFISRDPGWVE
Number of residues
1276
Molecular Weight
146871.005
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 D 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:8175689). 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 (PubMed:21483489). Recognition of SV2 by this toxin does not occur via SV2 glycosylation or its large extracellular loop 4 (PubMed:21483489). Another group does not find a convincing interaction with SV2 (PubMed:21632541). 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 (PubMed:19650874, PubMed:21483489, PubMed:21632541). 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 (PubMed:20704566, PubMed:21483489).
Specific Function
ganglioside GT1b 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 IDP19321
UniProtKB Entry NameBXD_CLOBO
PDB ID(s)2FPQ, 3N7J, 3OBR, 3OBT, 3OGG, 3RMX, 3RMY, 5BQM, 5BQN
General References
  1. Binz T, Kurazono H, Popoff MR, Eklund MW, Sakaguchi G, Kozaki S, Krieglstein K, Henschen A, Gill DM, Niemann H: Nucleotide sequence of the gene encoding Clostridium botulinum neurotoxin type D. Nucleic Acids Res. 1990 Sep 25;18(18):5556. [Article]
  2. Sunagawa H, Ohyama T, Watanabe T, Inoue K: The complete amino acid sequence of the Clostridium botulinum type D neurotoxin, deduced by nucleotide sequence analysis of the encoding phage d-16 phi genome. J Vet Med Sci. 1992 Oct;54(5):905-13. [Article]
  3. Moriishi K, Syuto B, Kubo S, Oguma K: Molecular diversity of neurotoxins from Clostridium botulinum type D strains. Infect Immun. 1989 Sep;57(9):2886-91. [Article]
  4. Yamasaki S, Baumeister A, Binz T, Blasi J, Link E, Cornille F, Roques B, Fykse EM, Sudhof TC, Jahn R, et al.: Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin. J Biol Chem. 1994 Apr 29;269(17):12764-72. [Article]
  5. Arndt JW, Chai Q, Christian T, Stevens RC: Structure of botulinum neurotoxin type D light chain at 1.65 A resolution: repercussions for VAMP-2 substrate specificity. Biochemistry. 2006 Mar 14;45(10):3255-62. [Article]

Associated Data

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