Grandi, Fabio; Sandal, Massimo; Guarguaglini, Giovanni; Capriotti, Emidio; Casadio, Rita; Samori, Bruno
Hierarchical mechanochemical switches in angiostatin
CHEMBIOCHEM, 7:1774-1782, NOV 2006

We wish to propose a novel mechanism by which the triggering of a biochemical signal can be controlled by the hierarchical coupling between a protein redox equilibrium and an external mechanical force. We have characterized this mechanochemical mechanism in angiostatin, and we have evidence that it can switch the access to partially unfolded structures of this protein. We have identified a metastable intermediate that is specifically accessible under thioredoxin-rich reducing conditions, like those met by angiostatin on the surface of a tumor cell. The structure of the same intermediate accounts for the unexplained antiangiogenic activity of angiostatin. These findings demonstrate a new link between redox biology and mechanically regulated processes.

DOI:10.1002/cbic.200600227

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