7QPT

Botulinum neurotoxin A4 cell binding domain in complex with GD1a oligosaccharide

Summary for 7QPT

• Entry DOI: 10.2210/pdb7qpt/pdb
• Descriptor: Neurotoxin type A, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose-(1-4)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: cell binding domain, receptor, oligosaccharide, neurotoxin, toxin
• Biological source: Clostridium botulinum
• Total number of polymer chains: 2
• Total formula weight: 103510.82

Authors

Gregory, K.S.,Acharya, K.R.,Liu, S.M.,Mojanaga, O.O. (deposition date: 2022-01-05, release date: 2022-03-16, Last modification date: 2024-11-06)

Primary citation

Gregory, K.S.,Mojanaga, O.O.,Liu, S.M.,Acharya, K.R.
Crystal Structures of Botulinum Neurotoxin Subtypes A4 and A5 Cell Binding Domains in Complex with Receptor Ganglioside.
Toxins, 14:-, 2022

PubMed Abstract: Botulinum neurotoxins (BoNT) cause the potentially fatal neuroparalytic disease botulism that arises due to proteolysis of a SNARE protein. Each BoNT is comprised of three domains: a cell binding domain (H), a translocation domain (H), and a catalytic (Zn endopeptidase) domain (LC). The H is responsible for neuronal specificity by targeting both a protein and ganglioside receptor at the neuromuscular junction. Although highly toxic, some BoNTs are commercially available as therapeutics for the treatment of a range of neuromuscular conditions. Here we present the crystal structures of two BoNT cell binding domains, H/A4 and H/A5, in a complex with the oligosaccharide of ganglioside, GD1a and GM1b, respectively. These structures, along with a detailed comparison with the previously reported apo-structures, reveal the conformational changes that occur upon ganglioside binding and the interactions involved.

PubMed: 35202156
DOI: 10.3390/toxins14020129

Experimental method

X-RAY DIFFRACTION (2.3 Å)