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

Proteolysis Lab, Molecular Biology Institute of Barcelona, CSIC, Barcelona Science Park c/Baldiri Reixac, 15-21, 08028 Barcelona (Spain)
Angewandte Chemie International Edition (Impact Factor: 11.26). 04/2012; 51(14):3340-4. DOI: 10.1002/anie.201108015
Source: PubMed


I'm your Venus: The crystal structure of the human methylamine-induced form of α(2) -macroglobulin (α(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 α(2) M.

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    • "To date, there are no crystal structures for native A 2 M. While there is a low resolution structure of methylamine-reacted A 2 M (a form of A 2 M wherein the anti-proteinase undergoes conformational changes similar to those elicited by targeted proteinases) [29], this conformation is known to be very different from that of the native A 2 M [30] [31], thereby complicating efforts to characterize oxidative events at the structural level. We therefore turned our focus to glutamine synthetase from Escherichia coli, for which several excellent crystal structures have been determined [32] [33] [34]. "
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