Bacterial mimicry of the eukaryotic innate immune system

Orateur : Andrea DESSEN (Institute of Structural Biology, Grenoble)

Alpha-2-macroglobulins (A2Ms) are plas ma 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 cellby trapping external proteases through a covalent interaction with an activated thioester. We have been able to structurally characterize the A2M from Salmonella typhimurium in different states of thioester activation. Our structures reveal thirteen domains whose arrangement displays high similarity to proteins involved in eukaryotic immune defense. 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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