Journal
STRUCTURE
Volume 21, Issue 9, Pages 1602-1611Publisher
CELL PRESS
DOI: 10.1016/j.str.2013.06.026
Keywords
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Funding
- Swedish Research Council [2010-5200]
- Wenner-Gren foundations
- Magnus Bergvalls foundation
- Swedish Foundation for Strategic research
- EMBO Long Term Fellowship [GA-2010-267146]
- EMBO Marie Curie Actions (EMBOCOFUND) [GA-2010-267146]
- NIH grants [8P51OD011103-51, 1R56AI097834-01, 1R01NS080833-01]
- Biostruct-X
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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.
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