A single point mutation expands the applicability of ostreolysin A6 in biomedicine.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 02 2023
07 02 2023
Historique:
received:
18
10
2022
accepted:
27
01
2023
entrez:
7
2
2023
pubmed:
8
2
2023
medline:
10
2
2023
Statut:
epublish
Résumé
An aegerolysin protein ostreolysin A6 (OlyA6) binds to cholesterol-complexed sphingomyelin and can be used for specific labelling of lipid rafts. In addition, OlyA6 interacts with even higher affinity with ceramide phosphoethanolamine (CPE), a sphingolipid that dominates in invertebrate cell membranes. In the presence of pleurotolysin B, a protein bearing the membrane-attack complex/perforin domain, OlyA6 forms pores in insect midgut cell membranes and acts as a potent bioinsecticide. It has been shown that a point mutation of glutamate 69 to alanine (E69A) allows OlyA6 to bind to cholesterol-free sphingomyelin. Using artificial lipid membranes and mammalian MDCK cells, we show that this mutation significantly enhances the interaction of OlyA6 with sphingomyelin and CPE, and allows recognition of these sphingolipids even in the absence of cholesterol. Our results suggest that OlyA6 mutant E69A could serve as complementary tool to detect and study cholesterol-associated and free sphingomyelin or CPE in membranes. However, the mutation does not improve the membrane-permeabilizing activity after addition of pleurotolysin B, which was confirmed in toxicity tests on insect and mammalian cell lines, and on Colorado potato beetle larvae.
Identifiants
pubmed: 36750638
doi: 10.1038/s41598-023-28949-7
pii: 10.1038/s41598-023-28949-7
pmc: PMC9905591
doi:
Substances chimiques
ostreolysin
0
Sphingomyelins
0
Cholesterol
97C5T2UQ7J
Membranes, Artificial
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2149Informations de copyright
© 2023. The Author(s).
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