The structure of α₁-antitrypsin is centered on β-sheet A (green) and the mobile reactive center loop (red). Polymer formation results from the Z variant of α₁-antitrypsin (Glu342Lys at P17; arrow) or mutations in the shutter domain (blue circle) that open β-sheet A to favor partial loop insertion and the formation of an unstable intermediate (M*) (10, 11). The patent β-sheet A can accept either the loop of another molecule, to form a dimer (D), which then extends into polymers (P), or else its own loop, to form a latent conformation (L). The individual molecules of α₁-antitrypsin within the polymer are colored red, yellow, and blue.