5LR0

Binding domain of Botulinum Neurotoxin DC in complex with SialylT

Summary for 5LR0

• Entry DOI: 10.2210/pdb5lr0/pdb
• Related: 4ISQ 4ISR
• Descriptor: Botulinum neurotoxin D/C protein, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose, beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose, ... (5 entities in total)
• Functional Keywords: botulnimun neurotoxin, carbohydrate binding, hydrolase
• Biological source: Clostridium botulinum
• Total number of polymer chains: 2
• Total formula weight: 101497.98

Authors

Berntsson, R.P.-A.,Stenmark, P. (deposition date: 2016-08-18, release date: 2017-08-30, Last modification date: 2024-01-10)

Primary citation

Zhang, S.,Berntsson, R.P.,Tepp, W.H.,Tao, L.,Johnson, E.A.,Stenmark, P.,Dong, M.
Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC.
Nat Commun, 8:1637-1637, 2017

PubMed Abstract: 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.

PubMed: 29158482
DOI: 10.1038/s41467-017-01534-z

Experimental method

X-RAY DIFFRACTION (2.59 Å)