Vibiro vulnificus hemolysin associates with gangliosides.
Animals
Bacterial Proteins
/ chemistry
Binding Sites
/ drug effects
CHO Cells
Cell Membrane
/ metabolism
Cholesterol
/ metabolism
Cricetulus
Gangliosides
/ pharmacology
Glycomics
/ methods
Hemolysin Proteins
/ chemistry
Microarray Analysis
Protein Binding
/ drug effects
Protein Conformation
Protein Multimerization
/ drug effects
Vibrio vulnificus
/ metabolism
Gangliosides
Hemolysin
Receptor
Vibrio vulnificus
Journal
BMC microbiology
ISSN: 1471-2180
Titre abrégé: BMC Microbiol
Pays: England
ID NLM: 100966981
Informations de publication
Date de publication:
30 03 2020
30 03 2020
Historique:
received:
16
06
2019
accepted:
20
03
2020
entrez:
2
4
2020
pubmed:
2
4
2020
medline:
7
4
2021
Statut:
epublish
Résumé
Vibrio vulnificus hemolysin (VVH) is a pore-forming toxin secreted by Vibrio vulnificus. Cellular cholesterol was believed to be the receptor for VVH, because cholesterol could bind to VVH and preincubation with cholesterol inhibited cytotoxicity. It has been reported that specific glycans such as N-acetyl-D-galactosamine and N-acetyl-D-lactosamine bind to VVH, however, it has not been known whether these glycans could inhibit the cytotoxicity of VVH without oligomer formation. Thus, to date, binding mechanisms of VVH to cellular membrane, including specific receptors have not been elucidated. We show here that VVH associates with ganglioside GM1a, Fucosyl-GM1, GD1a, GT1c, and GD1b by glycan array. Among them, GM1a could pulldown VVH. Moreover, the GD1a inhibited the cytotoxicity of VVH without the formation of oligomers. This is the first report of a molecule able to inhibit the binding of VVH to target cells without oligomerization of VVH.
Sections du résumé
BACKGROUND
Vibrio vulnificus hemolysin (VVH) is a pore-forming toxin secreted by Vibrio vulnificus. Cellular cholesterol was believed to be the receptor for VVH, because cholesterol could bind to VVH and preincubation with cholesterol inhibited cytotoxicity. It has been reported that specific glycans such as N-acetyl-D-galactosamine and N-acetyl-D-lactosamine bind to VVH, however, it has not been known whether these glycans could inhibit the cytotoxicity of VVH without oligomer formation. Thus, to date, binding mechanisms of VVH to cellular membrane, including specific receptors have not been elucidated.
RESULTS
We show here that VVH associates with ganglioside GM1a, Fucosyl-GM1, GD1a, GT1c, and GD1b by glycan array. Among them, GM1a could pulldown VVH. Moreover, the GD1a inhibited the cytotoxicity of VVH without the formation of oligomers.
CONCLUSION
This is the first report of a molecule able to inhibit the binding of VVH to target cells without oligomerization of VVH.
Identifiants
pubmed: 32228455
doi: 10.1186/s12866-020-01755-1
pii: 10.1186/s12866-020-01755-1
pmc: PMC7106661
doi:
Substances chimiques
Bacterial Proteins
0
Gangliosides
0
Hemolysin Proteins
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
69Subventions
Organisme : Japan Society for the Promotion of Science KAKENHI
ID : 18H02350
Pays : International
Organisme : Joint Research Project of the Research Institute for Microbial Diseases, the University of Osaka
ID : N/A
Pays : International
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