YopM of Yersinia enterocolitica specifically interacts with alpha1-antitrypsin without affecting the anti-protease activity

Microbiology. 2006 May;152(Pt 5):1327-35. doi: 10.1099/mic.0.28697-0.

Abstract

It was previously shown that alpha1-antitrypsin (AAT) interacts with the type III secreted (T3S) EspB and EspD proteins of enteropathogenic Escherichia coli (EPEC), resulting in reduced functionality of the proteins. To determine if AAT is also able to interact with T3S proteins of other pathogens, the binding of AAT to Yop proteins of Yersinia enterocolitica was analysed. AAT did not interact with YopB or YopD, which have functions in type III translocation similar to EspB and EspD in EPEC, but specifically interacts with YopM, a member of the leucine-rich repeat (LRR) family of proteins, in overlay and pull-down assays. To determine regions of YopM involved in AAT binding, various N- and C-terminally truncated versions of YopM were recombinantly expressed, and their ability to interact with AAT analysed. All versions tested were able to bind AAT, indicating that at least eight LRR of YopM are sufficient for AAT interaction. The main physiological role of AAT is to inhibit neutrophil elastase; however, elastase was efficiently inhibited by AAT in the presence and absence of YopM, indicating that YopM does not interfere with the anti-protease inhibition activity of AAT, and that the domain of AAT interacting with YopM is not identical to AAT's protease interaction domain. Furthermore, it was shown that elastase efficiently degrades YopM and other Yop proteins. The data suggest that AAT has additional functions in the host response against bacterial infections that are not related to its anti-protease activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Blotting, Western
  • Electrophoresis, Polyacrylamide Gel
  • Pancreatic Elastase / antagonists & inhibitors
  • Pancreatic Elastase / metabolism
  • Protein Interaction Mapping
  • Sequence Deletion
  • Yersinia enterocolitica / metabolism*
  • alpha 1-Antitrypsin / metabolism*

Substances

  • Bacterial Outer Membrane Proteins
  • alpha 1-Antitrypsin
  • yopM protein, Yersinia
  • Pancreatic Elastase