Functional characterization of an extended binding component of the actin-ADP-ribosylating C2 toxin detected in Clostridium botulinum strain (C) 2300.
Clostridium botulinum C2 toxin consists of the binding component C2II and the enzyme component C2I, which ADP-ribosylates G-actin of eukaryotic cells. Trypsin-activated C2II (C2IIa) forms heptamers that mediate cell binding and translocation of C2I from acidic endosomes into the cytosol of target cells. By genome sequencing of C. botulinum strain (C) 2300, we found that C2II from this strain carries a C-terminal extension of 129 amino acids, unlike its homologous counterparts from strains (C) 203U28, (C) 468, and (D) 1873. This extension shows a high similarity to the C-terminal receptor-binding domain of C2II and is presumably the result of a duplication of this domain. The C2II extension facilitates the binding to cell surface receptors, which leads to an increased intoxication efficiency compared to that of C2II proteins from other C. botulinum strains.
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, Albertstr 25, 79104 Freiburg, Germany.
Charlott
C
Sterthoff
Alexander E
AE
Lang
Carsten
C
Schwan
Andreas
A
Tauch
Klaus
K
Aktories
D000199:Actins / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001905:Botulinum Toxins / Q000235:genetics / Q000378:metabolism*; D003014:Clostridium botulinum / Q000201:enzymology* / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D020440:Gene Duplication; D016680:Genome, Bacterial; D008969:Molecular Sequence Data; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D000199:Actins; D004269:DNA, Bacterial; D000244:Adenosine Diphosphate; D011065:Poly(ADP-ribose) Polymerases; D001905:Botulinum Toxins; C096324:botulinum toxin type C