Molecular landscape of BoNT/B bound to a membrane-inserted synaptotagmin/ganglioside complex.
Cell Mol Life Sci
; 79(9): 496, 2022 Aug 25.
Article
in En
| MEDLINE
| ID: mdl-36006520
ABSTRACT
Botulinum neurotoxin serotype B (BoNT/B) uses two separate protein and polysialoglycolipid-binding pockets to interact with synaptotagmin 1/2 and gangliosides. However, an integrated model of BoNT/B bound to its neuronal receptors in a native membrane topology is still lacking. Using a panel of in silico and experimental approaches, we present here a new model for BoNT/B binding to neuronal membranes, in which the toxin binds to a preassembled synaptotagmin-ganglioside GT1b complex and a free ganglioside allowing a lipid-binding loop of BoNT/B to interact with the glycone part of the synaptotagmin-associated GT1b. Furthermore, our data provide molecular support for the decrease in BoNT/B sensitivity in Felidae that harbor the natural variant synaptotagmin2-N59Q. These results reveal multiple interactions of BoNT/B with gangliosides and support a novel paradigm in which a toxin recognizes a protein/ganglioside complex.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Synaptotagmin II
/
Gangliosides
Language:
En
Journal:
Cell Mol Life Sci
Journal subject:
BIOLOGIA MOLECULAR
Year:
2022
Type:
Article
Affiliation country:
France