Structure and activity of a functional derivative of Clostridium botulinum neurotoxin B.
J Struct Biol
; 174(1): 52-7, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-21078393
ABSTRACT
Botulinum neurotoxins (BoNTs) cause flaccid paralysis by inhibiting neurotransmission at cholinergic nerve terminals. BoNTs consist of three essential domains for toxicity the cell binding domain (Hc), the translocation domain (Hn) and the catalytic domain (LC). A functional derivative (LHn) of the parent neurotoxin B composed of Hn and LC domains was recombinantly produced and characterised. LHn/B crystallographic structure at 2.8Å resolution is reported. The catalytic activity of LHn/B towards recombinant human VAMP was analysed by substrate cleavage assay and showed a higher specificity for VAMP-1, -2 compared to VAMP-3. LHn/B also showed measurable activity in living spinal cord neurons. Despite lacking the Hc (cell-targeting) domain, LHn/B retained the capacity to internalize and cleave intracellular VAMP-1 and -2 when added to the cells at high concentration. These activities of the LHn/B fragment demonstrate the utility of engineered botulinum neurotoxin fragments as analytical tools to study the mechanisms of action of BoNT neurotoxins and of SNARE proteins.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Toxinas Botulínicas
/
Clostridium botulinum
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article