Determinants of pH-Dependent Modulation of Translocation in Dermonecrotic G-Protein-Deamidating Toxins

Cytotoxic necrotizing factors from E. coli (CNF1, CNF2) and Yersinia (CNFy) share N-terminal sequence similarity with Pasteurella multocida toxin (PMT). This common N-terminal region harbors the receptor-binding and translocation domains that mediate uptake and delivery of the C-terminal catalytic c...

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Main Authors: Tana L. Repella, Mengfei Ho, Brenda A. Wilson
Format: Article
Language:English
Published: MDPI AG 2013-06-01
Series:Toxins
Subjects:
Online Access:http://www.mdpi.com/2072-6651/5/6/1167
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author Tana L. Repella
Mengfei Ho
Brenda A. Wilson
author_facet Tana L. Repella
Mengfei Ho
Brenda A. Wilson
author_sort Tana L. Repella
collection DOAJ
description Cytotoxic necrotizing factors from E. coli (CNF1, CNF2) and Yersinia (CNFy) share N-terminal sequence similarity with Pasteurella multocida toxin (PMT). This common N-terminal region harbors the receptor-binding and translocation domains that mediate uptake and delivery of the C-terminal catalytic cargo domains into the host cytosol. Subtle variations in the N-terminal ~500 amino acids of CNFs and PMT could allow for selective recognition of cellular receptors and thus, selective target cell specificity. Through studies with cellular inhibitors, we have identified an additional novel function for this region in modulating responses of these toxin proteins to changes in pH during intoxication and delivery of the catalytic cargo domain into the cytosol.
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spelling doaj.art-796e4f44763d443e960320c10ca8833a2022-12-22T03:10:33ZengMDPI AGToxins2072-66512013-06-01561167117910.3390/toxins5061167Determinants of pH-Dependent Modulation of Translocation in Dermonecrotic G-Protein-Deamidating ToxinsTana L. RepellaMengfei HoBrenda A. WilsonCytotoxic necrotizing factors from E. coli (CNF1, CNF2) and Yersinia (CNFy) share N-terminal sequence similarity with Pasteurella multocida toxin (PMT). This common N-terminal region harbors the receptor-binding and translocation domains that mediate uptake and delivery of the C-terminal catalytic cargo domains into the host cytosol. Subtle variations in the N-terminal ~500 amino acids of CNFs and PMT could allow for selective recognition of cellular receptors and thus, selective target cell specificity. Through studies with cellular inhibitors, we have identified an additional novel function for this region in modulating responses of these toxin proteins to changes in pH during intoxication and delivery of the catalytic cargo domain into the cytosol.http://www.mdpi.com/2072-6651/5/6/1167cytotoxic necrotizing factorPasteurella multocida toxindermonecrotic toxinendosomal acidificationintoxicationdrug-deliverytoxin-based therapeutics
spellingShingle Tana L. Repella
Mengfei Ho
Brenda A. Wilson
Determinants of pH-Dependent Modulation of Translocation in Dermonecrotic G-Protein-Deamidating Toxins
Toxins
cytotoxic necrotizing factor
Pasteurella multocida toxin
dermonecrotic toxin
endosomal acidification
intoxication
drug-delivery
toxin-based therapeutics
title Determinants of pH-Dependent Modulation of Translocation in Dermonecrotic G-Protein-Deamidating Toxins
title_full Determinants of pH-Dependent Modulation of Translocation in Dermonecrotic G-Protein-Deamidating Toxins
title_fullStr Determinants of pH-Dependent Modulation of Translocation in Dermonecrotic G-Protein-Deamidating Toxins
title_full_unstemmed Determinants of pH-Dependent Modulation of Translocation in Dermonecrotic G-Protein-Deamidating Toxins
title_short Determinants of pH-Dependent Modulation of Translocation in Dermonecrotic G-Protein-Deamidating Toxins
title_sort determinants of ph dependent modulation of translocation in dermonecrotic g protein deamidating toxins
topic cytotoxic necrotizing factor
Pasteurella multocida toxin
dermonecrotic toxin
endosomal acidification
intoxication
drug-delivery
toxin-based therapeutics
url http://www.mdpi.com/2072-6651/5/6/1167
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