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 [ PUBMED:34970276 ]. However, A2M-like proteins were identified in pathogenic invasive bacteria and species that colonize higher eukaryotes. In human A2Ms … expand

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 [ PUBMED:34970276 ]. However, A2M-like proteins were identified in pathogenic invasive bacteria and species that colonize higher eukaryotes. In human A2Ms, this domain encompasses macroglobulin-like domain MG5 and 6 including bait region. In Salmonella enterica ser A2Ms, this domain encompasses MG7 and MG8 including the bait region [ PUBMED:25221932 PUBMED:22290936 ]. The bait region is cleaved by proteases, followed by a large conformational change that blocks the target protease within a cage-like complex. This model of protease entrapment is recognised as the Venus flytrap mechanism [ PUBMED:25221932 ].