Structure of a bacterial α2-macroglobulin reveals mimicry of eukaryotic innate immunity.
S.G.Wong,
A.Dessen.
ABSTRACT
Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad
range of proteases and are major components of the eukaryotic innate immune
system. Surprisingly, A2M-like proteins were identified in pathogenically
invasive bacteria and species that colonize higher eukaryotes. Bacterial A2Ms
are located in the periplasm where they are believed to provide protection to
the cell by trapping external proteases through a covalent interaction with an
activated thioester. Here we report the crystal structures and characterization
of Salmonella enterica ser. Typhimurium A2M in different states of thioester
activation. The structures reveal thirteen domains whose arrangement displays
high similarity to proteins involved in eukaryotic immune defence. A structural
lock mechanism maintains the stability of the buried thioester, a requirement
for its protease-trapping activity. These findings indicate that bacteria have
developed a rudimentary innate immune system whose mechanism mimics that of
eukaryotes.
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