Structural highlights
Function
[A2MG_HUMAN] Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.
Publication Abstract from PubMed
I'm your Venus: The crystal structure of the human methylamine-induced form of alpha(2) -macroglobulin (alpha(2) M) shows its large central cavity can accommodate two medium-sized proteinases (see structure, front part clipped off to better show central cavity). Twelve major entrances provide access for small substrates to the cavity and the still-active trapped "prey". The structure unveils the molecular basis of the unique "venus flytrap" mechanism of alpha(2) M.
The Crystal Structure of Human alpha(2) -Macroglobulin Reveals a Unique Molecular Cage.,Marrero A, Duquerroy S, Trapani S, Goulas T, Guevara T, Andersen GR, Navaza J, Sottrup-Jensen L, Gomis-Ruth FX Angew Chem Int Ed Engl. 2012 Jan 31. doi: 10.1002/anie.201108015. PMID:22290936[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Marrero A, Duquerroy S, Trapani S, Goulas T, Guevara T, Andersen GR, Navaza J, Sottrup-Jensen L, Gomis-Ruth FX. The Crystal Structure of Human alpha(2) -Macroglobulin Reveals a Unique Molecular Cage. Angew Chem Int Ed Engl. 2012 Jan 31. doi: 10.1002/anie.201108015. PMID:22290936 doi:10.1002/anie.201108015
