A conserved stable core structure in the passenger domain beta-helix of autotransporter virulence proteins

Biopolymers. 2008 May;89(5):420-7. doi: 10.1002/bip.20924.

Abstract

In Gram-negative bacteria, a wide variety of virulence factors are secreted via the autotransporter (AT) pathway. Intriguingly, there is no significant concentration of ATP in the periplasm, nor a proton gradient across the OM, so the energetic origin of efficient secretion of AT proteins is unknown. More than 97% of AT proteins are predicted to contain right-handed parallel beta-helical structure, and the three crystal structures available for AT passenger domains each contain a long right-handed parallel beta-helix. Previous studies have shown that pertactin, an AT from Bordetella pertussis, exhibits three-state folding and has a C-terminal stable core structure. Here, we show that Pet, an unrelated AT from Escherichia coli, also exhibits three-state unfolding and also has a stable core structure. Deletion mutants, mass spectrometry, and N-terminal sequencing demonstrate that the Pet stable core is also located near the C-terminus of the passenger domain. Moreover, sequence analysis suggests that three-state folding and a C-terminal stable core structure could be important general features of the biogenesis of AT proteins in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / genetics
  • Conserved Sequence
  • Electrophoresis, Polyacrylamide Gel
  • Endopeptidase K / chemistry
  • Enterotoxins / chemistry*
  • Enterotoxins / genetics
  • Escherichia coli / chemistry
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Guanidine / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Denaturation
  • Protein Folding*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Serine Endopeptidases
  • Virulence Factors / chemistry*
  • Virulence Factors / genetics
  • Virulence Factors, Bordetella / chemistry
  • Virulence Factors, Bordetella / genetics

Substances

  • Bacterial Outer Membrane Proteins
  • Bacterial Toxins
  • Enterotoxins
  • Escherichia coli Proteins
  • Virulence Factors
  • Virulence Factors, Bordetella
  • pertactin
  • heat-labile enterotoxin, E coli
  • Pet protein, E coli
  • Serine Endopeptidases
  • Endopeptidase K
  • Guanidine