Overview of hα2M action based on biochemical analysis. In native (hα2M)4, the four intact bait regions (black) are exposed in the enclosed cavity (prey chamber), while the thioester bonds (pink) and RBDs (gray ovals) are hidden. Monomer pairs 1 and 2, as well as 3 and 4, are disulfide-linked protomers (dashed green lines); pairs 1 and 3, as well as 2 and 4, are vicinal protomers; and pairs 1 and 4, as well as 2 and 3, are diagonally opposite protomers. Each protomer thus has a vicinal, a disulfide-linked, and an opposite protomer. The mechanism of action is illustrated in four steps that result in three states as described in the text.