Molecular landscape of BoNT/B bound to a membrane-inserted synaptotagmin/ganglioside complex

Archive ouverte

Ramirez-Franco, Jorge | Azzaz, Fodil | Sangiardi, Marion | Ferracci, Géraldine | Youssouf, Fahamoe | Popoff, Michel Robert | Seagar, Michael | Lévêque, Christian | Fantini, Jacques | El Far, Oussama

Edité par CCSD ; Springer Verlag -

International audience. 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 synaptotagminganglioside GT1b complex and a free ganglioside allowing a lipid-binding loop of 2 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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion