6zvn: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 8: | Line 8: | ||
== Function == | == Function == | ||
[[https://www.uniprot.org/uniprot/Q8GR96_CLOBO Q8GR96_CLOBO]] | [[https://www.uniprot.org/uniprot/Q8GR96_CLOBO Q8GR96_CLOBO]] | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Botulinum neurotoxins (BoNTs) can be used therapeutically to treat a wide range of neuromuscular and neurological conditions. A collection of natural BoNT variants exists which can be classified into serologically distinct serotypes (BoNT/B), and further divided into subtypes (BoNT/B1, B2, ...). BoNT subtypes share a high degree of sequence identity within the same serotype yet can display large variation in toxicity. One such example is BoNT/B2, which was isolated from Clostridium botulinum strain 111 in a clinical case of botulism, and presents a 10-fold lower toxicity than BoNT/B1. In an effort to understand the molecular mechanisms behind this difference in potency, we here present the crystal structures of BoNT/B2 in complex with the ganglioside receptor GD1a, and with the human synaptotagmin I protein receptor. We show, using receptor-binding assays, that BoNT/B2 has a slightly higher affinity for GD1a than BoNT/B1, and confirm its considerably weaker affinity for its protein receptors. Although the overall receptor-binding mechanism is conserved for both receptors, structural analysis suggests the lower affinity of BoNT/B2 is the result of key substitutions, where hydrophobic interactions important for synaptotagmin-binding are replaced by polar residues. This study provides a template to drive the development of future BoNT therapeutic molecules centered on assessing the natural subtype variations in receptor-binding that appears to be one of the principal stages driving toxicity. | |||
Structural and Biochemical Characterization of Botulinum Neurotoxin Subtype B2 Binding to Its Receptors.,Davies JR, Masuyer G, Stenmark P Toxins (Basel). 2020 Sep 17;12(9). pii: toxins12090603. doi:, 10.3390/toxins12090603. PMID:32957706<ref>PMID:32957706</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6zvn" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]] | *[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]] | ||
*[[Synaptotagmin 3D structures|Synaptotagmin 3D structures]] | *[[Synaptotagmin 3D structures|Synaptotagmin 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
