Mechanistic link between β barrel assembly and the initiation of autotransporter secretion

Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):E938-47. doi: 10.1073/pnas.1219076110. Epub 2013 Feb 19.

Abstract

Autotransporters are bacterial virulence factors that contain an N-terminal extracellular ("passenger") domain and a C-terminal β barrel ("β") domain that anchors the protein to the outer membrane. The β domain is required for passenger domain secretion, but its exact role in autotransporter biogenesis is unclear. Here we describe insights into the function of the β domain that emerged from an analysis of mutations in the Escherichia coli O157:H7 autotransporter EspP. We found that the G1066A and G1081D mutations slightly distort the structure of the β domain and delay the initiation of passenger domain translocation. Site-specific photocrosslinking experiments revealed that the mutations slow the insertion of the β domain into the outer membrane, but do not delay the binding of the β domain to the factor that mediates the insertion reaction (the Bam complex). Our results demonstrate that the β domain does not simply target the passenger domain to the outer membrane, but promotes translocation when it reaches a specific stage of assembly. Furthermore, our results provide evidence that the Bam complex catalyzes the membrane integration of β barrel proteins in a multistep process that can be perturbed by minor structural defects in client proteins.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / physiology
  • Escherichia coli O157 / genetics
  • Escherichia coli O157 / pathogenicity*
  • Escherichia coli O157 / physiology*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / physiology*
  • Genes, Bacterial
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Mutagenesis, Site-Directed
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Transport
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*
  • Virulence Factors / genetics
  • Virulence Factors / physiology

Substances

  • Bacterial Outer Membrane Proteins
  • BamA protein, E coli
  • BamD protein, E coli
  • Escherichia coli Proteins
  • Multiprotein Complexes
  • Virulence Factors
  • EspP protein, E coli
  • Serine Endopeptidases