title: Autolysis of calpain large subunit inducing irreversible dissociation of stoichiometric heterodimer of calpain.
abstract: Calpain, a calcium dependent cysteine protease, consists of a catalytic large subunit and a regulatory small subunit. Two models have been proposed to explain calpain activation: an autolysis model and a dissociation model. In the autolysis model, the autolyzed form is the active species, which is sensitized to Ca2+. In the dissociation model, dissociated large subunit is the active species. We have reported that the Ca2+ concentration regulates reversible dissociation of subunits. We found further that in chicken micro/m-calpain autolysis of the large subunit induces irreversible dissociation from the small subunit as well as activation. So we could propose a new mechanism for activation of the calpain by combining our findings. Our model insists that autolyzed large subunit remains dissociated from the small subunit even after the removal of Ca2+ to keep it sensitized to Ca2+. This model could be expanded to other calpains and give a new perspective on calpain activation.
authors.affiliation: Department of Molecular Biology, Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan. hrs-ktgk@ja2.so-net.ne.jp
authors.forename: H
authors.initials: H
authors.lastname: Kitagaki
authors.forename: S
authors.initials: S
authors.lastname: Tomioka
authors.forename: T
authors.initials: T
authors.lastname: Yoshizawa
authors.forename: H
authors.initials: H
authors.lastname: Sorimachi
authors.forename: T C
authors.initials: TC
authors.lastname: Saido
authors.forename: S
authors.initials: S
authors.lastname: Ishiura
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium; D002154:Calpain / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D002645:Chickens; D019281:Dimerization; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D008969:Molecular Sequence Data
chemical_list: D002154:Calpain; D002118:Calcium