Crystal structures of botulinum neurotoxin DC in complex with its protein receptors synaptotagmin I and II.
Botulinum neurotoxins (BoNTs) can cause paralysis at exceptionally low concentrations and include seven serotypes (BoNT/A-G). The chimeric BoNT/DC toxin has a receptor binding domain similar to the same region in BoNT/C. However, BoNT/DC does not share protein receptor with BoNT/C. Instead, it shares synaptotagmin (Syt) I and II as receptors with BoNT/B, despite their low sequence similarity. Here, we present the crystal structures of the binding domain of BoNT/DC in complex with the recognition domains of its protein receptors, Syt-I and Syt-II. The structures reveal that BoNT/DC possesses a Syt binding site, distinct from the established Syt-II binding site in BoNT/B. Structure-based mutagenesis further shows that hydrophobic interactions play a key role in Syt binding. The structures suggest that the BoNT/DC ganglioside binding sites are independent of the protein receptor binding site. Our results reveal the remarkable versatility in the receptor recognition of the BoNTs.
Department of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, Sweden.
Ronnie Per-Arne
RP
Berntsson
Lisheng
L
Peng
Linda Marie
LM
Svensson
Min
M
Dong
Pål
P
Stenmark
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001905:Botulinum Toxins / Q000737:chemistry*; D003014:Clostridium botulinum; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D051381:Rats; D040681:Structural Homology, Protein; D050863:Synaptotagmin I / Q000737:chemistry*; D050861:Synaptotagmin II / Q000737:chemistry*
C494310:SYT1 protein, human; D050863:Synaptotagmin I; D050861:Synaptotagmin II; C494264:Syt2 protein, rat; C096325:botulinum toxin type D; D001905:Botulinum Toxins; C096324:botulinum toxin type C