Inhibition and Entrapment of Aspartic Proteinases by α2-Macroglobulin

The Crystal Structure of Human α2‐Macroglobulin Reveals a Unique Molecular Cage

“…Thereby, induced α 2 M is recognized by specific cell‐surface receptors, which do not recognize native α 2 M. The complex is internalized by endocytosis and degraded in the lysosomes, thus ensuring clearance of the inhibitor and its cargo from the circulation within minutes of complex formation. Owing to its general inhibitory activity against proteinases, α 2 M has universal physiological functions and imbalance of its activity contributes to several major human diseases, such as Alzheimer’s disease, AIDS, inflammatory diseases, tumor growth and progression, and cardiovascular disease 10–14…”

The Crystal Structure of Human α2‐Macroglobulin Reveals a Unique Molecular Cage

“…Owing to its general inhibitory activity against proteinases, a 2 M has universal physiological functions and imbalance of its activity contributes to several major human diseases, such as Alzheimers disease, AIDS, inflammatory diseases, tumor growth and progression, and cardiovascular disease. [10][11][12][13][14] To shed light on the molecular features of the intricate working mechanism of a 2 M, we determined the crystal structure of human MA-induced a 2 M (a 2 M-MA) to 4.3 resolution (see the Supporting Information). The human a 2 M-MA monomer consists of 11 domains (Figure 1 a) and is shaped like a distorted equilateral triangular prism with a side of approximately 110 (Figure 1 b,c).…”