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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Format: | Article |
Language: | English |
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MDPI AG
2013-06-01
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Series: | Toxins |
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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. |
first_indexed | 2024-04-13T00:27:52Z |
format | Article |
id | doaj.art-796e4f44763d443e960320c10ca8833a |
institution | Directory Open Access Journal |
issn | 2072-6651 |
language | English |
last_indexed | 2024-04-13T00:27:52Z |
publishDate | 2013-06-01 |
publisher | MDPI AG |
record_format | Article |
series | Toxins |
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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