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

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 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.
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https://www.hal.inserm.fr/inserm-03780828
Contributor : Oussama El Far Connect in order to contact the contributor
Submitted on : Monday, September 19, 2022 - 5:08:34 PM
Last modification on : Friday, September 23, 2022 - 10:05:10 AM

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Jorge Ramirez-Franco, Fodil Azzaz, Marion Sangiardi, Géraldine Ferracci, Fahamoe Youssouf, et al.. Molecular landscape of BoNT/B bound to a membrane-inserted synaptotagmin/ganglioside complex. Cellular and Molecular Life Sciences, Springer Verlag, 2022, 79 (9), pp.496. ⟨10.1007/s00018-022-04527-4⟩. ⟨inserm-03780828⟩

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