Autotransporter structure reveals intra-barrel cleavage followed by conformational changes

Nat Struct Mol Biol. 2007 Dec;14(12):1214-20. doi: 10.1038/nsmb1322. Epub 2007 Nov 11.

Abstract

Autotransporters are virulence factors produced by Gram-negative bacteria. They consist of two domains, an N-terminal 'passenger' domain and a C-terminal beta-domain. beta-domains form beta-barrel structures in the outer membrane while passenger domains are translocated into the extracellular space. In some autotransporters, the two domains are separated by proteolytic cleavage. Using X-ray crystallography, we solved the 2.7-A structure of the post-cleavage state of the beta-domain of EspP, an autotransporter produced by Escherichia coli strain O157:H7. The structure consists of a 12-stranded beta-barrel with the passenger domain-beta-domain cleavage junction located inside the barrel pore, approximately midway between the extracellular and periplasmic surfaces of the outer membrane. The structure reveals an unprecedented intra-barrel cleavage mechanism and suggests that two conformational changes occur in the beta-domain after cleavage, one conferring increased stability on the beta-domain and another restricting access to the barrel pore.

Publication types

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

MeSH terms

  • Crystallography, X-Ray
  • Escherichia coli O157 / chemistry
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Hydrolysis
  • Point Mutation
  • Protein Conformation
  • Serine Endopeptidases / chemistry*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Static Electricity

Substances

  • Escherichia coli Proteins
  • EspP protein, E coli
  • Serine Endopeptidases

Associated data

  • PDB/2QOM