BXG_CLOBO
ID BXG_CLOBO Reviewed; 1297 AA.
AC Q60393;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Botulinum neurotoxin type G;
DE Short=BoNT/G {ECO:0000303|PubMed:8268233};
DE AltName: Full=Bontoxilysin-G;
DE Contains:
DE RecName: Full=Botulinum neurotoxin G light chain;
DE Short=LC;
DE EC=3.4.24.69 {ECO:0000269|PubMed:7910017};
DE Contains:
DE RecName: Full=Botulinum neurotoxin G heavy chain;
DE Short=HC;
DE Flags: Precursor;
GN Name=botG;
OS Clostridium botulinum.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=1491;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=113 / 30 / NCFB 3012 / Type G;
RX PubMed=8268233; DOI=10.1016/0167-4781(93)90020-e;
RA Campbell K., Collins M.D., East A.K.;
RT "Nucleotide sequence of the gene coding for Clostridium botulinum
RT (Clostridium argentinense) type G neurotoxin: genealogical comparison with
RT other clostridial neurotoxins.";
RL Biochim. Biophys. Acta 1216:487-491(1993).
RN [2]
RP IDENTIFICATION OF TOXIN, SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN TYPE
RP G), HOST RANGE, EPIDEMIOLOGY, AND POSSIBLE RELEASE AS SINGLE CHAIN.
RC STRAIN=89 / BL 1353 /Type G;
RX PubMed=4922309;
RA Gimenez D.F., Ciccarelli A.S.;
RT "Another type of Clostridium botulinum.";
RL Zentralbl. Bakteriol. 215:221-224(1970).
RN [3]
RP SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN TYPE G), HOST RANGE,
RP EPIDEMIOLOGY, AND POSSIBLE RELEASE AS SINGLE CHAIN.
RC STRAIN=89 / BL 1353 /Type G;
RX PubMed=74236; DOI=10.1128/aem.34.6.843-848.1977;
RA Ciccarelli A.S., Whaley D.N., McCroskey L.M., Gimenez D.F.,
RA Dowell V.R. Jr., Hatheway C.L.;
RT "Cultural and physiological characteristics of Clostridium botulinum type G
RT and the susceptibility of certain animals to its toxin.";
RL Appl. Environ. Microbiol. 34:843-848(1977).
RN [4]
RP HOST RANGE, AND EPIDEMIOLOGY.
RX DOI=10.1099/00207713-38-4-375;
RA Sue J.C., Hatheway C.L., Steigerwalt A.G., Brenner D.J.;
RT "Clostridium argentinense sp. nov.: a genetically homogeneous group
RT composed of all Strains of Clostridium botulinum toxin type G and some
RT nontoxigenic strains previously identified as Clostridium subterminale or
RT Clostridium hastiforme.";
RL Int. J. Syst. Bacteriol. 38:375-381(1988).
RN [5]
RP FUNCTION (BOTULINUM NEUROTOXIN G LIGHT CHAIN), IDENTIFICATION OF SUBSTRATE,
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN G LIGHT
RP CHAIN).
RX PubMed=7910017; DOI=10.1006/bbrc.1994.1526;
RA Yamasaki S., Binz T., Hayashi T., Szabo E., Yamasaki N., Eklund M.,
RA Jahn R., Niemann H.;
RT "Botulinum neurotoxin type G proteolyses the Ala81-Ala82 bond of rat
RT synaptobrevin 2.";
RL Biochem. Biophys. Res. Commun. 200:829-835(1994).
RN [6]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE G AND BOTULINUM NEUROTOXIN G HEAVY
RP CHAIN), IDENTIFICATION OF HOST RECEPTOR (BOTULINUM NEUROTOXIN TYPE G), AND
RP INTERACTION WITH HOST SYT1 AND SYT2.
RC STRAIN=Type G;
RX PubMed=15123599; DOI=10.1074/jbc.m403945200;
RA Rummel A., Karnath T., Henke T., Bigalke H., Binz T.;
RT "Synaptotagmins I and II act as nerve cell receptors for botulinum
RT neurotoxin G.";
RL J. Biol. Chem. 279:30865-30870(2004).
RN [7]
RP FUNCTION (BOTULINUM NEUROTOXIN B HEAVY CHAIN), INTERACTION WITH HOST SYT1
RP AND SYT2, AND MUTAGENESIS OF MET-1126; LEU-1191; GLN-1200; TYR-1262 AND
RP TRP-1268.
RC STRAIN=Type G;
RX PubMed=17185412; DOI=10.1073/pnas.0609713104;
RA Rummel A., Eichner T., Weil T., Karnath T., Gutcaits A., Mahrhold S.,
RA Sandhoff K., Proia R.L., Acharya K.R., Bigalke H., Binz T.;
RT "Identification of the protein receptor binding site of botulinum
RT neurotoxins B and G proves the double-receptor concept.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:359-364(2007).
RN [8]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE G), FUNCTION (BOTULINUM NEUROTOXIN G
RP HEAVY CHAIN), AND MUTAGENESIS OF GLN-1200 AND TRP-1268.
RX PubMed=19650874; DOI=10.1111/j.1471-4159.2009.06298.x;
RA Rummel A., Haefner K., Mahrhold S., Darashchonak N., Holt M., Jahn R.,
RA Beermann S., Karnath T., Bigalke H., Binz T.;
RT "Botulinum neurotoxins C, E and F bind gangliosides via a conserved binding
RT site prior to stimulation-dependent uptake with botulinum neurotoxin F
RT utilising the three isoforms of SV2 as second receptor.";
RL J. Neurochem. 110:1942-1954(2009).
RN [9] {ECO:0007744|PDB:1ZB7}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-443 IN COMPLEX WITH ZINC, AND
RP COFACTOR.
RX PubMed=16008342; DOI=10.1021/bi0505924;
RA Arndt J.W., Yu W., Bi F., Stevens R.C.;
RT "Crystal structure of botulinum neurotoxin type G light chain: serotype
RT divergence in substrate recognition.";
RL Biochemistry 44:9574-9580(2005).
RN [10] {ECO:0007744|PDB:3MPP}
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 867-1297, FUNCTION (BOTULINUM
RP NEUROTOXIN B HEAVY CHAIN), DOMAIN, GANGLIOSIDE-BINDING, AND MUTAGENESIS OF
RP 1080-SER--TRP-1084.
RC STRAIN=Type G;
RX PubMed=20507178; DOI=10.1021/bi100412v;
RA Schmitt J., Karalewitz A., Benefield D.A., Mushrush D.J., Pruitt R.N.,
RA Spiller B.W., Barbieri J.T., Lacy D.B.;
RT "Structural analysis of botulinum neurotoxin type G receptor binding.";
RL Biochemistry 49:5200-5205(2010).
RN [11] {ECO:0007744|PDB:2VXR}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 863-1297, FUNCTION (BOTULINUM
RP NEUROTOXIN B HEAVY CHAIN), SUBUNIT, AND DOMAIN.
RC STRAIN=Type G;
RX PubMed=20219474; DOI=10.1016/j.jmb.2010.02.041;
RA Stenmark P., Dong M., Dupuy J., Chapman E.R., Stevens R.C.;
RT "Crystal structure of the botulinum neurotoxin type G binding domain:
RT insight into cell surface binding.";
RL J. Mol. Biol. 397:1287-1297(2010).
CC -!- FUNCTION: [Botulinum neurotoxin type G]: Botulinum toxin causes flaccid
CC paralysis by inhibiting neurotransmitter (acetylcholine) release from
CC the presynaptic membranes of nerve terminals of the eukaryotic host
CC skeletal and autonomic nervous system, with frequent heart or
CC respiratory failure (PubMed:15123599). Precursor of botulinum
CC neurotoxin G which has 2 coreceptors; complex polysialylated
CC gangliosides found on neural tissue and specific membrane-anchored
CC proteins found in synaptic vesicles (PubMed:15123599). Receptor
CC proteins are exposed on host presynaptic cell membrane during
CC neurotransmitter release, when the toxin heavy chain (HC) binds to
CC them. Upon synaptic vesicle recycling the toxin is taken up via the
CC endocytic pathway. When the pH of the toxin-containing endosome drops a
CC structural rearrangement occurs so that the N-terminus of the HC forms
CC pores that allows the light chain (LC) to translocate into the cytosol.
CC Once in the cytosol the disulfide bond linking the 2 subunits is
CC reduced and LC cleaves its target protein on synaptic vesicles,
CC preventing their fusion with the cytoplasmic membrane and thus
CC neurotransmitter release (By similarity). Binds to host peripheral
CC neuronal presynaptic membranes via synaptotagmins 1 and 2 (SYT1 and
CC SYT2) (PubMed:15123599). Toxin binds to the membrane proximal extra-
CC cytoplasmic region of SYT1 and SYT2 that is transiently exposed outside
CC of cells during exocytosis; exogenous gangliosides do not enhance
CC binding and subsequent uptake of toxin into host cells
CC (PubMed:15123599). Toxin activity can be blocked by the appropriate
CC synaptotagmin protein fragments in cell culture (PubMed:15123599).
CC {ECO:0000250|UniProtKB:P0DPI0, ECO:0000269|PubMed:15123599}.
CC -!- FUNCTION: [Botulinum neurotoxin G light chain]: Has proteolytic
CC activity. After translocation into the eukaryotic host cytosol acts as
CC a zinc endopeptidase that cleaves synaptobrevins-1, -2 and -3 (also
CC called VAMP1, VAMP2 and VAMP3) (PubMed:7910017). Hydrolyzes the '81-
CC Ala-|-Ala-82' bond of VAMP2, and probably also the equivalent 'Ala-|-
CC Ala' sites in VAMP1 and VAMP3 (PubMed:7910017). Has low activity on
CC A.californica synaptobrevin and none on D.melanogaster synaptobrevin or
CC cellubrevin, have a slightly different sequence (PubMed:7910017).
CC {ECO:0000269|PubMed:7910017}.
CC -!- FUNCTION: [Botulinum neurotoxin G heavy chain]: Responsible for host
CC cell targeting and translocation of light chain (LC) into host cytosol.
CC Composed of 3 subdomains; the translocation domain (TD), and N-terminus
CC and C-terminus of the receptor-binding domain (N-RBD, C-RBD). The RBD
CC is responsible for the adherence of the toxin to the cell surface. It
CC simultaneously recognizes 2 coreceptors; polysialated gangliosides and
CC the receptor proteins SYT1 and SYT2 in close proximity on host synaptic
CC vesicles (PubMed:17185412). The N-terminus of the TD wraps an extended
CC belt around the perimeter of the LC, protecting Zn(2+) in the active
CC site; it may also prevent premature LC dissociation from the
CC translocation channel and protect toxin prior to translocation (By
CC similarity). The TD inserts into synaptic vesicle membrane to allow
CC translocation into the host cytosol (By similarity). Has 2 coreceptors;
CC complex gangliosides found primarily on neural tissue and host
CC synaptotagmin-1 and -2 (SYT1 and SYT2) which bind to separate sites at
CC the tip of the HC (PubMed:17185412). HC alone binds to host receptors
CC SYT1 and SYT2; C-RBD interacts with host SYT2 (PubMed:15123599). Has
CC equal affinity for SYT1 and SYT2; gangliosides are not required for (or
CC only very slightly improve) binding to a membrane-anchored receptor
CC fragment (PubMed:17185412, PubMed:20219474). Has also been shown to
CC only bind SYT1; the assay methods were different (PubMed:20507178).
CC Binds ganglioside GT1b (PubMed:20507178). Significantly decreases
CC uptake and toxicity of whole BoNT/B and BoNT/G (PubMed:19650874).
CC {ECO:0000250|UniProtKB:P0DPI0, ECO:0000269|PubMed:15123599,
CC ECO:0000269|PubMed:17185412, ECO:0000269|PubMed:19650874,
CC ECO:0000269|PubMed:20219474, ECO:0000269|PubMed:20507178}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Limited hydrolysis of proteins of the neuroexocytosis
CC apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on
CC small molecule substrates.; EC=3.4.24.69;
CC Evidence={ECO:0000269|PubMed:7910017};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:16008342};
CC Note=Binds 1 zinc ion per subunit (PubMed:16008342).
CC {ECO:0000269|PubMed:16008342};
CC -!- SUBUNIT: Heterodimer; disulfide-linked heterodimer of a light chain
CC (LC) and a heavy chain (HC). The LC has the proteolytic/pharmacological
CC activity, while the N- and C-termini of the HC mediate channel
CC formation and toxin binding, respectively. Interacts with host
CC receptors synaptotagmin-1 and -2 (SYT1 and SYT2) (PubMed:15123599,
CC PubMed:17185412, PubMed:20219474). {ECO:0000269|PubMed:15123599,
CC ECO:0000269|PubMed:17185412, ECO:0000269|PubMed:20219474}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin type G]: Secreted
CC {ECO:0000269|PubMed:74236, ECO:0000305|PubMed:4922309}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin G light chain]: Secreted
CC {ECO:0000305|PubMed:74236}. Host cytoplasm, host cytosol
CC {ECO:0000305|PubMed:7910017}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin G heavy chain]: Secreted
CC {ECO:0000305|PubMed:74236}. Host synapse, host presynaptic cell
CC membrane {ECO:0000250|UniProtKB:P0DPI0}. Host cytoplasmic vesicle, host
CC secretory vesicle, host synaptic vesicle membrane
CC {ECO:0000250|UniProtKB:P0DPI0}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- DOMAIN: [Botulinum neurotoxin G light chain]: Has protease activity
CC (PubMed:7910017). {ECO:0000269|PubMed:7910017}.
CC -!- DOMAIN: [Botulinum neurotoxin G heavy chain]: Has 3 functional domains.
CC The translocation domain (TD) which probably forms membrane channels to
CC allow light chain (LC) into the host cytosol (Probable). The C-terminal
CC receptor-binding domain (RBD) has 2 further subdomains, N-RBD (Hcn) and
CC C-RBD (Hcc) (PubMed:20507178, PubMed:20219474). The N-terminus of the
CC TD wraps an extended belt around the perimeter of the LC, protecting
CC Zn(2+) in the active site and may be a pseudosubstrate inhibitor which
CC serves as an intramolecular chaperone for the LC prior to its
CC translocation into the host cytosol (By similarity). The RBD binds
CC transiently exposed coreceptors on the host presynaptic cell membrane
CC (Probable). {ECO:0000250|UniProtKB:P0DPI0, ECO:0000269|PubMed:20219474,
CC ECO:0000269|PubMed:20507178, ECO:0000269|PubMed:7910017,
CC ECO:0000305|PubMed:15123599}.
CC -!- MISCELLANEOUS: There are seven antigenically distinct forms of
CC botulinum neurotoxin: Types A, B, C, D, E, F, and G; new subtypes are
CC quite frequent.
CC -!- MISCELLANEOUS: Botulism poisoning is usually food-borne, either by
CC ingesting toxin or bacterial-contaminated food, or less frequently by
CC inhalation poisoning. In both cases the neurotoxin binds to the apical
CC surface of epithelial cells in the gut or airway. Toxin undergoes
CC receptor-mediated endocytosis (using a different receptor than on
CC target nerve cells), transcytosis across the epithelial cells and
CC release into the general circulation. Once in the general circulation
CC it binds to its target cells. {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- MISCELLANEOUS: Type G toxin has been isolated from soil samples and
CC human autopsy specimens but has not been clearly implicated as the
CC cause of human paralytic illness or death (Ref.4). Strain 89 was
CC isolated from soil in Mendoza province, Argentiana (PubMed:4922309).
CC Administration of strain 89 toxin to mouse, chicken, guinea pig and
CC rhesus monkeys causes botulism symptoms and in most cases death, while
CC dog and sheep show no signs of botulism (PubMed:74236). In the original
CC report 5-fold higher levels of toxin caused botulism and death in sheep
CC (PubMed:4922309). {ECO:0000269|PubMed:4922309,
CC ECO:0000269|PubMed:74236, ECO:0000305|Ref.4}.
CC -!- MISCELLANEOUS: Trypsinization of purified toxin increases its toxicity,
CC suggesting it is released as a single chain (PubMed:4922309,
CC PubMed:74236). {ECO:0000305|PubMed:4922309, ECO:0000305|PubMed:74236}.
CC -!- SIMILARITY: Belongs to the peptidase M27 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=BotDB - A Database Resource for Clostridial
CC Neurotoxins;
CC URL="https://botdb.abcc.ncifcrf.gov/";
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DR EMBL; X74162; CAA52275.1; -; Genomic_DNA.
DR PIR; S39791; S39791.
DR PDB; 1ZB7; X-ray; 2.35 A; A=1-443.
DR PDB; 2VXR; X-ray; 1.90 A; A=863-1297.
DR PDB; 3MPP; X-ray; 1.98 A; G=867-1297.
DR PDBsum; 1ZB7; -.
DR PDBsum; 2VXR; -.
DR PDBsum; 3MPP; -.
DR SMR; Q60393; -.
DR DIP; DIP-60790N; -.
DR IntAct; Q60393; 3.
DR MINT; Q60393; -.
DR DrugBank; DB13899; Equine Botulinum Neurotoxin G Immune FAB2.
DR MEROPS; M27.002; -.
DR UniLectin; Q60393; -.
DR ABCD; Q60393; 27 sequenced antibodies.
DR BRENDA; 3.4.24.69; 1462.
DR Reactome; R-HSA-5250989; Toxicity of botulinum toxin type G (botG).
DR EvolutionaryTrace; Q60393; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044161; C:host cell cytoplasmic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0044156; C:host cell junction; IEA:UniProtKB-KW.
DR GO; GO:0044231; C:host cell presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0008320; F:protein transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0046929; P:negative regulation of neurotransmitter secretion; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1120.10; -; 1.
DR InterPro; IPR000395; Bot/tetX_LC.
DR InterPro; IPR036248; Clostridium_toxin_transloc.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR011065; Kunitz_inhibitor_STI-like_sf.
DR InterPro; IPR013104; Toxin_rcpt-bd_C.
DR InterPro; IPR012928; Toxin_rcpt-bd_N.
DR InterPro; IPR012500; Toxin_trans.
DR Pfam; PF01742; Peptidase_M27; 1.
DR Pfam; PF07951; Toxin_R_bind_C; 1.
DR Pfam; PF07953; Toxin_R_bind_N; 1.
DR Pfam; PF07952; Toxin_trans; 1.
DR PRINTS; PR00760; BONTOXILYSIN.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF50386; SSF50386; 1.
DR SUPFAM; SSF58091; SSF58091; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Host cell membrane; Host cytoplasm;
KW Host cytoplasmic vesicle; Host membrane; Host synapse; Hydrolase;
KW Lipid-binding; Membrane; Metal-binding; Metalloprotease; Neurotoxin;
KW Protease; Secreted; Toxin; Virulence; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT CHAIN 2..1297
FT /note="Botulinum neurotoxin type G"
FT /id="PRO_0000444922"
FT CHAIN 2..442
FT /note="Botulinum neurotoxin G light chain"
FT /id="PRO_0000029227"
FT CHAIN 443..1297
FT /note="Botulinum neurotoxin G heavy chain"
FT /id="PRO_0000029228"
FT REGION 446..862
FT /note="Translocation domain (TD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 488..537
FT /note="Belt"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 868..1073
FT /note="N-terminus of receptor binding domain (N-RBD)"
FT /evidence="ECO:0000269|PubMed:20219474,
FT ECO:0000269|PubMed:20507178"
FT REGION 1089..1297
FT /note="C-terminus of receptor binding domain (C-RBD)"
FT /evidence="ECO:0000269|PubMed:20219474,
FT ECO:0000269|PubMed:20507178"
FT MOTIF 1266..1269
FT /note="Host ganglioside-binding motif"
FT /evidence="ECO:0000305|PubMed:17185412"
FT ACT_SITE 231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 230
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:16008342, ECO:0007744|PDB:1ZB7"
FT BINDING 234
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:16008342, ECO:0007744|PDB:1ZB7"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16008342,
FT ECO:0007744|PDB:1ZB7"
FT SITE 1268
FT /note="Ganglioside-binding site"
FT /evidence="ECO:0000305|PubMed:17185412"
FT DISULFID 436..450
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0, ECO:0000305"
FT MUTAGEN 1080..1084
FT /note="SSLYW->EERYK: Improves solubility of isolated heavy
FT chain (HC), used for crystallization."
FT /evidence="ECO:0000269|PubMed:20507178"
FT MUTAGEN 1126
FT /note="M->D: Significantly decreased binding of HC to host
FT SYT1 and SYT2 independent of gangliosides."
FT /evidence="ECO:0000269|PubMed:17185412"
FT MUTAGEN 1191
FT /note="L->R: Significantly decreased binding of HC to host
FT SYT1 and SYT2 independent of gangliosides."
FT /evidence="ECO:0000269|PubMed:17185412"
FT MUTAGEN 1200
FT /note="Q->E: Significantly decreased binding of HC to host
FT SYT1 and SYT2 independent of gangliosides."
FT /evidence="ECO:0000269|PubMed:17185412"
FT MUTAGEN 1200
FT /note="Q->K: Decreased binding of HC to host SYT1 and SYT2
FT independent of gangliosides; whole toxin is less toxic.
FT Dramatically decreased toxicity; when associated with L-
FT 1268. HC no longer inhibits whole-toxin uptake and
FT toxicity."
FT /evidence="ECO:0000269|PubMed:17185412,
FT ECO:0000269|PubMed:19650874"
FT MUTAGEN 1262
FT /note="Y->F: Slightly increased binding of HC to host SYT1
FT and SYT2 in presence of gangliosides."
FT /evidence="ECO:0000269|PubMed:17185412"
FT MUTAGEN 1268
FT /note="W->L: Gangliosides no longer increase HC affinity
FT for SYT1 or SYT2; whole toxin about significantly less
FT toxic. Dramatically decreased toxicity; when associated
FT with K-1200. In mice without complex gangliosides no change
FT compared to wild-type protein. HC no longer inhibits whole-
FT toxin uptake and toxicity."
FT /evidence="ECO:0000269|PubMed:17185412,
FT ECO:0000269|PubMed:19650874"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 34..40
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 69..74
FT /evidence="ECO:0007829|PDB:1ZB7"
FT TURN 76..79
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 82..99
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 103..114
FT /evidence="ECO:0007829|PDB:1ZB7"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 191..194
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 199..208
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 224..239
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 266..273
FT /evidence="ECO:0007829|PDB:1ZB7"
FT TURN 277..279
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 282..303
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 308..313
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 316..327
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 341..353
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 357..364
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 377..381
FT /evidence="ECO:0007829|PDB:1ZB7"
FT TURN 388..390
FT /evidence="ECO:0007829|PDB:1ZB7"
FT TURN 393..395
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 400..402
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 406..411
FT /evidence="ECO:0007829|PDB:1ZB7"
FT TURN 413..415
FT /evidence="ECO:0007829|PDB:1ZB7"
FT HELIX 417..419
FT /evidence="ECO:0007829|PDB:1ZB7"
FT TURN 425..427
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 428..432
FT /evidence="ECO:0007829|PDB:1ZB7"
FT STRAND 870..876
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 879..882
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 889..892
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 897..899
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 905..911
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 916..919
FT /evidence="ECO:0007829|PDB:2VXR"
FT TURN 922..924
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 927..930
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 933..940
FT /evidence="ECO:0007829|PDB:2VXR"
FT HELIX 946..948
FT /evidence="ECO:0007829|PDB:2VXR"
FT HELIX 949..954
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 956..964
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 967..974
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 977..983
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 989..995
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 998..1002
FT /evidence="ECO:0007829|PDB:3MPP"
FT STRAND 1010..1016
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1020..1026
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1029..1035
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1046..1054
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1061..1072
FT /evidence="ECO:0007829|PDB:2VXR"
FT HELIX 1076..1086
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1097..1099
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1105..1113
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1116..1121
FT /evidence="ECO:0007829|PDB:2VXR"
FT HELIX 1122..1124
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1126..1131
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1134..1136
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1141..1143
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1150..1155
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1174..1184
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1186..1191
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1196..1200
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1202..1206
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1216..1219
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1229..1236
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1239..1248
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1260..1267
FT /evidence="ECO:0007829|PDB:2VXR"
FT HELIX 1268..1272
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1275..1277
FT /evidence="ECO:0007829|PDB:2VXR"
FT STRAND 1286..1289
FT /evidence="ECO:0007829|PDB:2VXR"
SQ SEQUENCE 1297 AA; 149146 MW; 306CF54CF3973C3B CRC64;
MPVNIKXFNY NDPINNDDII MMEPFNDPGP GTYYKAFRII DRIWIVPERF TYGFQPDQFN
ASTGVFSKDV YEYYDPTYLK TDAEKDKFLK TMIKLFNRIN SKPSGQRLLD MIVDAIPYLG
NASTPPDKFA ANVANVSINK KIIQPGAEDQ IKGLMTNLII FGPGPVLSDN FTDSMIMNGH
SPISEGFGAR MMIRFCPSCL NVFNNVQENK DTSIFSRRAY FADPALTLMH ELIHVLHGLY
GIKISNLPIT PNTKEFFMQH SDPVQAEELY TFGGHDPSVI SPSTDMNIYN KALQNFQDIA
NRLNIVSSAQ GSGIDISLYK QIYKNKYDFV EDPNGKYSVD KDKFDKLYKA LMFGFTETNL
AGEYGIKTRY SYFSEYLPPI KTEKLLDNTI YTQNEGFNIA SKNLKTEFNG QNKAVNKEAY
EEISLEHLVI YRIAMCKPVM YKNTGKSEQC IIVNNEDLFF IANKDSFSKD LAKAETIAYN
TQNNTIENNF SIDQLILDND LSSGIDLPNE NTEPFTNFDD IDIPVYIKQS ALKKIFVDGD
SLFEYLHAQT FPSNIENLQL TNSLNDALRN NNKVYTFFST NLVEKANTVV GASLFVNWVK
GVIDDFTSES TQKSTIDKVS DVSIIIPYIG PALNVGNETA KENFKNAFEI GGAAILMEFI
PELIVPIVGF FTLESYVGNK GHIIMTISNA LKKRDQKWTD MYGLIVSQWL STVNTQFYTI
KERMYNALNN QSQAIEKIIE DQYNRYSEED KMNINIDFND IDFKLNQSIN LAINNIDDFI
NQCSISYLMN RMIPLAVKKL KDFDDNLKRD LLEYIDTNEL YLLDEVNILK SKVNRHLKDS
IPFDLSLYTK DTILIQVFNN YISNISSNAI LSLSYRGGRL IDSSGYGATM NVGSDVIFND
IGNGQFKLNN SENSNITAHQ SKFVVYDSMF DNFSINFWVR TPKYNNNDIQ TYLQNEYTII
SCIKNDSGWK VSIKGNRIIW TLIDVNAKSK SIFFEYSIKD NISDYINKWF SITITNDRLG
NANIYINGSL KKSEKILNLD RINSSNDIDF KLINCTDTTK FVWIKDFNIF GRELNATEVS
SLYWIQSSTN TLKDFWGNPL RYDTQYYLFN QGMQNIYIKY FSKASMGETA PRTNFNNAAI
NYQNLYLGLR FIIKKASNSR NINNDNIVRE GDYIYLNIDN ISDESYRVYV LVNSKEIQTQ
LFLAPINDDP TFYDVLQIKK YYEKTTYNCQ ILCEKDTKTF GLFGIGKFVK DYGYVWDTYD
NYFCISQWYL RRISENINKL RLGCNWQFIP VDEGWTE
