Interaction of Epsilon Toxin with the Plasma Membrane: The Role of Amino Acids Y42, Y43 and H162

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2022 Nov 10

PMID 36356007

Authors

Skye Marshall

Beth McGill

Helen Morcrette

C Peter Winlove

Catalin Chimerel

Peter G Petrov

Monika Bokori-Brown

Affiliations

Soon will be listed here.

Abstract

epsilon toxin (Etx) is a pore forming toxin that causes enterotoxaemia in ruminants and may be a cause of multiple sclerosis in humans. To date, most in vitro studies of Etx have used the Madin-Darby canine kidney (MDCK) cell line. However, studies using Chinese hamster ovary (CHO) cells engineered to express the putative Etx receptor, myelin and lymphocyte protein (MAL), suggest that amino acids important for Etx activity differ between species. In this study, we investigated the role of amino acids Y42, Y43 and H162, previously identified as important in Etx activity towards MDCK cells, in Etx activity towards CHO-human MAL (CHO-hMAL) cells, human red blood cells (hRBCs) and synthetic bilayers using site-directed mutants of Etx. We show that in CHO-hMAL cells Y42 is critical for Etx binding and not Y43 as in MDCK cells, indicating that surface exposed tyrosine residues in the receptor binding domain of Etx impact efficiency of cell binding to MAL-expressing cells in a species-specific manner. We also show that Etx mutant H162A was unable to lyse CHO-hMAL cells, lysed hRBCs, whilst it was able to form pores in synthetic bilayers, providing evidence of the complexity of Etx pore formation in different lipid environments.

Citing Articles

Epsilon Toxin from Induces the Generation of Extracellular Vesicles in HeLa Cells Overexpressing Myelin and Lymphocyte Protein.

Dorca-Arevalo J, Santana-Ruiz A, Torrejon-Escribano B, Martin-Satue M, Blasi J Toxins (Basel). 2024; 16(12.

PMID: 39728783 PMC: 11728497. DOI: 10.3390/toxins16120525.

The Molecular Architecture and Mode of Action of ε-Toxin.

Titball R Toxins (Basel). 2024; 16(4).

PMID: 38668605 PMC: 11053738. DOI: 10.3390/toxins16040180.

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