Botulinum neurotoxin type C cleaves a single Lys-Ala bond within the carboxyl-terminal region of syntaxins.
Botulinum neurotoxin serotype C (BoNT/C) is a 150-kDa protein produced by Clostridium botulinum, which causes animal botulism. In contrast to the other botulinum neurotoxins that contain one atom of zinc, highly purified preparations of BoNT/C bind two atoms of zinc per toxin molecule. BoNT/C is a zinc-endopeptidase that cleaves syntaxin 1A at the Lys253-Ala254 and syntaxin 1B at the Lys252-Ala253 peptide bonds, only when they are inserted into a lipid bilayer. The other Lys-Ala bond present within the carboxyl-terminal region is not hydrolyzed. Syntaxin isoforms 2 and 3 are also cleaved by BoNT/C, while syntaxin 4 is resistant. These data suggest that BoNT/C recognizes a specific spatial organization of syntaxin, adopted upon membrane insertion, which brings a selected Lys-Ala peptide bond of its carboxyl-terminal region to the active site of this novel metalloproteinase.
Schiavo
G
G
Centro Consiglio Nazionale delle Ricerche Biomembrane, Università di Padova, Italy.
Shone
C C
CC
Bennett
M K
MK
Scheller
R H
RH
Montecucco
C
C
D000409:Alanine; D000595:Amino Acid Sequence; D000818:Animals; D001905:Botulinum Toxins / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D008239:Lysine; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D050765:Qa-SNARE Proteins; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism; D050827:Syntaxin 1; D015032:Zinc / Q000737:chemistry
D008051:Lipid Bilayers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D050765:Qa-SNARE Proteins; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D008666:Metalloendopeptidases; D001905:Botulinum Toxins; D015032:Zinc; D008239:Lysine; D000409:Alanine