The extent and fate of many biological processes are drastically affected by the stresses and strains that are exerted during their development. To understand the behavior of these processes also the force as a physical variable must be taken into account. A mechanical tension can alter the functional states of proteins and activate processes. We have obtained evidences of 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 mechanism in angiostatin, where the access to partially unfolded structures is controlled by mechanochemical switches. We have identified a metastable intermediate that is specifically accessible in the thioredoxin-rich reducing conditions like those met by angiostatin on the surface of a tumor cell. The structure of the same intermediate accounts for unexplained data on the antiangiogenic activity of angiostatin. These findings demonstrate a new link between redox biology and mechanically regulated processes.
The mechanochemical coupling of redox and force switches in the regulation of protein functional states .
SAMORI', BRUNO
2005
Abstract
The extent and fate of many biological processes are drastically affected by the stresses and strains that are exerted during their development. To understand the behavior of these processes also the force as a physical variable must be taken into account. A mechanical tension can alter the functional states of proteins and activate processes. We have obtained evidences of 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 mechanism in angiostatin, where the access to partially unfolded structures is controlled by mechanochemical switches. We have identified a metastable intermediate that is specifically accessible in the thioredoxin-rich reducing conditions like those met by angiostatin on the surface of a tumor cell. The structure of the same intermediate accounts for unexplained data on the antiangiogenic activity of angiostatin. These findings demonstrate a new link between redox biology and mechanically regulated processes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.