2VXR

Crystal Structure of the Botulinum Neurotoxin serotype G binding domain

Summary for 2VXR

• Entry DOI: 10.2210/pdb2vxr/pdb
• Related: 1ZB7
• Descriptor: BOTULINUM NEUROTOXIN TYPE G, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: toxin, hydrolase, neurotoxin, ganglioside, protease, receptor, secreted, botulinum, binding domain, metalloprotease
• Biological source: CLOSTRIDIUM BOTULINUM
• Total number of polymer chains: 1
• Total formula weight: 56660.76

Authors

Stenmark, P.,Dupuy, J.,Stevens, R.C. (deposition date: 2008-07-08, release date: 2009-07-07, Last modification date: 2023-12-13)

Primary citation

Stenmark, P.,Dong, M.,Dupuy, J.,Chapman, E.R.,Stevens, R.C.
Crystal Structure of the Botulinum Neurotoxin Type G Binding Domain: Insight Into Cell Surface Binding.
J.Mol.Biol., 397:1287-, 2010

PubMed Abstract: Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-A X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent.

PubMed: 20219474
DOI: 10.1016/J.JMB.2010.02.041

Experimental method

X-RAY DIFFRACTION (1.9 Å)