6ZVN

Botulinum neurotoxin B2 binding domain in complex with human synaptotagmin I


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.259 

wwPDB Validation 3D Report Full Report



Literature

Structural and Biochemical Characterization of Botulinum Neurotoxin Subtype B2 Binding to Its Receptors.

Davies, J.R.Masuyer, G.Stenmark, P.

(2020) Toxins (Basel) 12

  • DOI: 10.3390/toxins12090603
  • Primary Citation of Related Structures:  
    6ZVM, 6ZVN

  • PubMed Abstract: 
  • 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 fur ...

    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.


    Organizational Affiliation

    Department of Experimental Medical Science, Lund University, SE-221 00 Lund, Sweden.



Macromolecules
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Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
NeurotoxinAAA438Clostridium botulinumMutation(s): 0 
Gene Names: bontb
Find proteins for Q8GR96 (Clostridium botulinum)
Explore Q8GR96 
Go to UniProtKB:  Q8GR96
Protein Feature View
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 2
MoleculeChainsSequence LengthOrganismDetailsImage
Synaptotagmin-1BBB21Homo sapiensMutation(s): 0 
Gene Names: SYT1SVP65SYT
Find proteins for P21579 (Homo sapiens)
Explore P21579 
Go to UniProtKB:  P21579
NIH Common Fund Data Resources
PHAROS  P21579
Protein Feature View
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.259 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.677α = 90
b = 82.528β = 90
c = 106.7γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DIALSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History 

  • Version 1.0: 2020-10-14
    Type: Initial release