TAILIEUCHUNG - Báo cáo khoa học: Interaction between catalytically inactive calpain and calpastatin Evidence for its occurrence in stimulated cells

Conformational changes in the calpain molecule following interaction with natural ligands can be monitored by the binding of a specific monoclonal antibody directed against the catalytic domain of the protease. None of these conformational states showed catalytic activity and probably repre-sent intermediate forms preceding the active enzyme state. | iFEBS Journal Interaction between catalytically inactive calpain and calpastatin Evidence for its occurrence in stimulated cells Monica Averna Roberto Stifanese Roberta De Tullio Enrico Defranchi Franca Salamino Edon Melloni and Sandro Pontremoli Department of ExperimentalMedicine DIMES Section of Biochemistry and Centre of Excellence for BiomedicalResearch CEBR University of Genova Italy Keywords activation calcium calpain calpastatin conformational states Correspondence S. Pontremoli DIMES-Section of Biochemistry Viale Benedetto XV 1-16132 Genova Italy Fax 39 010518 343 Tel 39 010353 8128 E-mail pontremoli@ Received 9 January 2006 accepted 15 February 2006 doi Conformational changes in the calpain molecule following interaction with natural ligands can be monitored by the binding of a specific monoclonal antibody directed against the catalytic domain of the protease. None of these conformational states showed catalytic activity and probably represent intermediate forms preceding the active enzyme state. In its native inactive conformation calpain shows very low affinity for this monoclonal antibody whereas on binding to the ligands Ca2 substrate or calpasta-tin the affinity increases up to 10-fold with calpastatin being the most effective. This methodology was also used to show that calpain undergoes similar conformational changes in intact cells exposed to stimuli that induce either a rise in intracellular Ca2 or extensive diffusion of calpast-atin into the cytosol without affecting Ca2 homeostasis. The fact that the changes in the calpain state are also observed under the latter conditions indicates that calpastatin availability in the cytosol is the triggering event for calpain-calpastatin interaction which is presumably involved in the control of the extent of calpain activation through translocation to specific sites of action. In recent years information has accumulated on the 3D structure of q-calpain and m-calpain

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