5lr0

Publication Abstract from PubMed

Botulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A-G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in mice deficient in complex gangliosides. The co-crystal structure of BoNT/DC with sialyl-Thomsen-Friedenreich antigen (Sialyl-T) suggests that BoNT/DC recognizes only the sialic acid, but not other moieties in gangliosides. Using liposome flotation assays, we demonstrate that an extended loop in BoNT/DC directly interacts with lipid membranes, and the co-occurring sialic acid binding and loop-membrane interactions mediate the recognition of gangliosides in membranes by BoNT/DC. These findings reveal a unique mechanism for cell membrane recognition and demonstrate that BoNT/DC can use a broad range of sialic acid-containing moieties as co-receptors.

Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC.,Zhang S, Berntsson RP, Tepp WH, Tao L, Johnson EA, Stenmark P, Dong M Nat Commun. 2017 Nov 21;8(1):1637. doi: 10.1038/s41467-017-01534-z. PMID:29158482^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.