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Diphtheria01:28

Diphtheria

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Diphtheria is an acute, toxin-mediated infectious disease that primarily affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, a Gram-positive, pleomorphic rod that lacks spore-forming capability and exhibits a characteristic club-shaped morphology under microscopic examination. While C. diphtheriae can asymptomatically colonize mucosal surfaces, clinical disease manifests only when the bacterial strain is lysogenized by a specific β-corynephage. This phage...
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Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
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Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
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Bacteriophages, or phages, are viruses that specifically infect bacteria, utilizing their genetic material to hijack host cellular machinery for replication. DNA bacteriophages employ single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) genomes. These phages exhibit diverse replication strategies and host interactions, influencing their ecological roles and applications in biotechnology and medicine.ssDNA BacteriophagesssDNA phages, with their small genomes, utilize unique strategies to...
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Detection of Toxin Translocation into the Host Cytosol by Surface Plasmon Resonance
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Diphtheria toxin conformational switching at acidic pH.

Oneda Leka1, Francesca Vallese, Marco Pirazzini

  • 1Department of Biomedical Sciences, University of Padua, Italy.

The FEBS Journal
|March 18, 2014
PubMed
Summary

Diphtheria toxin (DT) undergoes structural changes at acidic pH, exposing hydrophobic regions. This structural rearrangement prepares the toxin for insertion into cell membranes to deliver its toxic payload.

Keywords:
Diphtheria toxin translocationbicellescrystal structuremembrane channelsmembrane insertion

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Area of Science:

  • Structural biology
  • Biochemistry
  • Molecular biology

Background:

  • Diphtheria toxin (DT) is internalized into the cytosol to exert its function.
  • The mechanism of toxin translocation across membranes is not fully understood.
  • Acidic pH in endosomes triggers structural changes in DT.

Purpose of the Study:

  • To elucidate the structural mechanism of Diphtheria toxin translocation.
  • To determine the crystal structure of DT at acidic pH.

Main Methods:

  • X-ray crystallography of Diphtheria toxin at acidic pH.
  • Crystallization in the presence of bicelles to mimic lipid bilayers.

Main Results:

  • The crystal structure of DT at acidic pH was determined.
  • Low pH induced unfolding of TH2, TH3, and TH4 α-helices.
  • A hydrophobic surface involving TH5 and TH8 α-helices was exposed, likely for membrane insertion.

Conclusions:

  • Acidic pH triggers a conformational change in Diphtheria toxin, exposing hydrophobic regions.
  • These exposed regions are poised for insertion into the lipid bilayer.
  • The findings provide insights into the molecular mechanism of toxin entry into the cytosol.