title: Structural analysis of botulinum neurotoxin type G receptor binding .
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: John
authors.initials: J
authors.lastname: Schmitt
authors.forename: Andrew
authors.initials: A
authors.lastname: Karalewitz
authors.forename: Desirée A
authors.initials: DA
authors.lastname: Benefield
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Mushrush
authors.forename: Rory N
authors.initials: RN
authors.lastname: Pruitt
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Spiller
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Barbieri
authors.forename: D Borden
authors.initials: DB
authors.lastname: Lacy
mesh_terms: 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*
chemical_list: D005732:Gangliosides; D011956:Receptors, Cell Surface; C488535:botulinum toxin type G; D001905:Botulinum Toxins