4ISQ

Binding domain of Botulinum neurotoxin DC in complex with human synaptotagmin I

Summary for 4ISQ

• Entry DOI: 10.2210/pdb4isq/pdb
• Related: 4ISR
• Descriptor: Neurotoxin, Synaptotagmin-1, SULFATE ION, ... (5 entities in total)
• Functional Keywords: membrane binding, synaptotagmin and ganglioside binding, toxin
• Biological source: Clostridium botulinum; More
• Cellular location: Cytoplasmic vesicle, secretory vesicle membrane ; Single-pass membrane protein : P21579
• Total number of polymer chains: 6
• Total formula weight: 160269.62

Authors

Berntsson, R.P.-A.,Peng, L.,Svensson, L.M.,Dong, M.,Stenmark, P. (deposition date: 2013-01-17, release date: 2013-08-14, Last modification date: 2024-02-28)

Primary citation

Berntsson, R.P.,Peng, L.,Svensson, L.M.,Dong, M.,Stenmark, P.
Crystal Structures of Botulinum Neurotoxin DC in Complex with Its Protein Receptors Synaptotagmin I and II.
Structure, 21:1602-1611, 2013

PubMed Abstract: 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.

PubMed: 23932591
DOI: 10.1016/j.str.2013.06.026

Experimental method

X-RAY DIFFRACTION (2.65 Å)