The interaction of synaptic vesicle-associated membrane protein/synaptobrevin with botulinum neurotoxins D and F.
Botulinum neurotoxins type D and F are zinc-endopeptidases with a unique specificity for VAMP/synaptobrevin, an essential component of the exocytosis apparatus. VAMP contains two copies of a nine residue motif, termed V1 and V2, which are determinants of the interaction with tetanus and botulinum B and G neurotoxins. Here, we show that V1 plays a major role in VAMP recognition by botulinum neurotoxins D and F and that V2 is also involved in F binding. Site-directed mutagenesis of V1 and V2 indicates that different residues are the determinants of the VAMP interaction with the two endopeptidases. The study of the VAMP-neurotoxins interaction suggest a pairing of the V1 and V2 segments.
Pellizzari
R
R
Centro CNR Biomembrane, Dipartimento di Scienze Biomediche, Università di Padova, Italy.
Mason
S
S
Shone
C C
CC
Montecucco
C
C
D000818:Animals; D001905:Botulinum Toxins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009994:Osmolar Concentration; D011485:Protein Binding; D050683:R-SNARE Proteins; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism*
D008565:Membrane Proteins; D050683:R-SNARE Proteins; D011994:Recombinant Proteins; C096325:botulinum toxin type D; D001905:Botulinum Toxins; C096321:botulinum toxin type F