Structural analysis of botulinum neurotoxin type G receptor binding .
Botulinum neurotoxin (BoNT) binds peripheral neurons at the neuromuscular junction through a dual-receptor mechanism that includes interactions with ganglioside and protein receptors. The receptor identities vary depending on BoNT serotype (A-G). BoNT/B and BoNT/G bind the luminal domains of synaptotagmin I and II, homologous synaptic vesicle proteins. We observe conditions under which BoNT/B binds both Syt isoforms, but BoNT/G binds only SytI. Both serotypes bind ganglioside G(T1b). The BoNT/G receptor-binding domain crystal structure provides a context for examining these binding interactions and a platform for understanding the physiological relevance of different Syt receptor isoforms in vivo.
Schmitt
John
J
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Karalewitz
Andrew
A
Benefield
Desirée A
DA
Mushrush
Darren J
DJ
Pruitt
Rory N
RN
Spiller
Benjamin W
BW
Barbieri
Joseph T
JT
Lacy
D Borden
DB
D001905:Botulinum Toxins / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005732:Gangliosides / Q000378:metabolism; D005822:Genetic Vectors; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D005732:Gangliosides; D011956:Receptors, Cell Surface; C488535:botulinum toxin type G; D001905:Botulinum Toxins