Determinants of pH-dependent modulation of translocation in dermonecrotic G-protein-deamidating toxins

Tana L. Repella, Mengfei Ho, Brenda A. Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1167-1179
Number of pages13
JournalToxins
Volume5
Issue number6
DOIs
StatePublished - Jun 14 2013

Keywords

  • Cytotoxic necrotizing factor
  • Dermonecrotic toxin
  • Drug-delivery
  • Endosomal acidification
  • Intoxication
  • Pasteurella multocida toxin
  • Toxin-based therapeutics

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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