Change search
ReferencesLink to record
Permanent link

Direct link
Crystal Structure of the Botulinum Neurotoxin Type G Binding Domain: Insight into Cell Surface Binding
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Show others and affiliations
2010 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 397, no 5, 1287-1297 p.Article in journal (Refereed) Published
Abstract [en]

Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-angstrom 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.

Place, publisher, year, edition, pages
2010. Vol. 397, no 5, 1287-1297 p.
Keyword [en]
botulinum, neurotoxin, synaptotagmin, ganglioside, toxin
National Category
Natural Sciences Biochemistry and Molecular Biology Structural Biology
Research subject
Biochemistry; Structural Biology
URN: urn:nbn:se:su:diva-50129DOI: 10.1016/j.jmb.2010.02.041ISI: 000276983300013OAI: diva2:380596
The Wenner-Gren FoundationSwedish Foundation for Strategic Research , ICA08-0001

authorCount :5

Available from: 2010-12-21 Created: 2010-12-21 Last updated: 2013-09-10

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Stenmark, Pål
By organisation
Department of Biochemistry and Biophysics
In the same journal
Journal of Molecular Biology
Natural SciencesBiochemistry and Molecular BiologyStructural Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 23 hits
ReferencesLink to record
Permanent link

Direct link