The inverse autotransporter intimin exports its passenger domain via a hairpin intermediate

J Biol Chem. 2015 Jan 16;290(3):1837-49. doi: 10.1074/jbc.M114.604769. Epub 2014 Dec 8.

Abstract

Autotransporter proteins comprise a large family of virulence factors that consist of a β-barrel translocation unit and an extracellular effector or passenger domain. The β-barrel anchors the protein to the outer membrane of Gram-negative bacteria and facilitates the transport of the passenger domain onto the cell surface. By inserting an epitope tag into the N terminus of the passenger domain of the inverse autotransporter intimin, we generated a mutant defective in autotransport. Using this stalled mutant, we could show that (i) at the time point of stalling, the β-barrel appears folded; (ii) the stalled autotransporter is associated with BamA and SurA; (iii) the stalled intimin is decorated with large amounts of SurA; (iv) the stalled autotransporter is not degraded by periplasmic proteases; and (v) inverse autotransporter passenger domains are translocated by a hairpin mechanism. Our results suggest a function for the BAM complex not only in insertion and folding of the β-barrel but also for passenger translocation.

Keywords: Adhesin; Bacterial Pathogenesis; Intimin, Type Ve Secretion, Autotransporter, beta Barrel Protein, Hairpin; Membrane Protein; Microbial Pathogenesis; Microbiology; Outer Membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / chemistry
  • Adhesins, Bacterial / physiology*
  • Biological Transport
  • Cell Membrane / metabolism
  • Cloning, Molecular
  • Cross-Linking Reagents / chemistry
  • Epitopes / chemistry
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / physiology*
  • HeLa Cells
  • Humans
  • Microscopy, Fluorescence
  • Molecular Chaperones / chemistry
  • Mutagenesis, Site-Directed
  • Mutation
  • Peptide Hydrolases / chemistry
  • Protein Binding
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Surface Properties

Substances

  • Adhesins, Bacterial
  • Cross-Linking Reagents
  • Epitopes
  • Escherichia coli Proteins
  • Molecular Chaperones
  • eaeA protein, E coli
  • Peptide Hydrolases