Assembly of an atypical α-macroglobulin complex from Pseudomonas aeruginosa

Sci Rep. 2018 Jan 11;8(1):527. doi: 10.1038/s41598-017-18083-6.


Alpha-2-macroglobulins (A2Ms) are large spectrum protease inhibitors that are major components of the eukaryotic immune system. Pathogenic and colonizing bacteria, such as the opportunistic pathogen Pseudomonas aeruginosa, also carry structural homologs of eukaryotic A2Ms. Two types of bacterial A2Ms have been identified: Type I, much like the eukaryotic form, displays a conserved thioester that is essential for protease targeting, and Type II, which lacks the thioester and to date has been poorly studied despite its ubiquitous presence in Gram-negatives. Here we show that MagD, the Type II A2M from P. aeruginosa that is expressed within the six-gene mag operon, specifically traps a target protease despite the absence of the thioester motif, comforting its role in protease inhibition. In addition, analytical ultracentrifugation and small angle scattering show that MagD forms higher order complexes with proteins expressed in the same operon (MagA, MagB, and MagF), with MagB playing the key stabilization role. A P. aeruginosa strain lacking magB cannot stably maintain MagD in the bacterial periplasm, engendering complex disruption. This suggests a regulated mechanism of Mag complex formation and stabilization that is potentially common to numerous Gram-negative organisms, and that plays a role in periplasm protection from proteases during infection or colonization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Operon
  • Pregnancy-Associated alpha 2-Macroglobulins / chemistry
  • Pregnancy-Associated alpha 2-Macroglobulins / genetics
  • Pregnancy-Associated alpha 2-Macroglobulins / metabolism*
  • Protein Multimerization*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism*


  • Bacterial Proteins
  • Pregnancy-Associated alpha 2-Macroglobulins