Crystal structures of botulinum neurotoxin DC in complex with its protein receptors synaptotagmin I and II

Structure. 2013 Sep 3;21(9):1602-11. doi: 10.1016/j.str.2013.06.026. Epub 2013 Aug 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Botulinum Toxins / chemistry*
  • Clostridium botulinum
  • Crystallography, X-Ray
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Interaction Domains and Motifs
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Rats
  • Structural Homology, Protein
  • Synaptotagmin I / chemistry*
  • Synaptotagmin II / chemistry*


  • SYT1 protein, human
  • Synaptotagmin I
  • Synaptotagmin II
  • Syt2 protein, rat
  • botulinum toxin type D
  • Botulinum Toxins
  • botulinum toxin type C

Associated data

  • PDB/4ISQ
  • PDB/4ISR