Title | Calpastatin subdomains A and C are activators of calpain. |
Publication Type | Journal Article |
Year of Publication | 2002 |
Authors | Tompa, P., Z. Mucsi, G. Orosz, and P. Friedrich |
Journal | J Biol Chem |
Volume | 277 |
Issue | 11 |
Pagination | 9022-6 |
Date Published | 2002 Mar 15 |
ISSN | 0021-9258 |
Keywords | Amino Acid Sequence, Animals, Calcium, Calcium-Binding Proteins, Calpain, Enzyme Activation, Humans, Molecular Sequence Data, Peptide Fragments, Rats |
Abstract | The inhibitory domains of calpastatin contain three highly conserved regions, A, B, and C, of which A and C bind calpain in a strictly Ca(2+)-dependent manner but have no inhibitory activity whereas region B inhibits calpain on its own. We synthesized the 19-mer oligopeptides corresponding to regions A and C of human calpastatin domain I and tested their effect on human erythrocyte mu-calpain and rat m-calpain. The two peptides significantly activate both calpains: the Ca(2+) concentration required for half-maximal activity is lowered from 4.3 to 2.4 microm for mu-calpain and from 250 to 140 microm for m-calpain. The EC(50) concentration of the peptides is 7.5 microm for mu-calpain and 25 microm for m-calpain. It is noteworthy that at low Ca(2+) concentrations (1-2 microm for mu-calpain and 70-110 microm for m-calpain) both enzymes are activated about 10-fold by the peptides. Based on these findings, it is suggested that calpastatin fragments may have a role in calpain activation in vivo. Furthermore, these activators open new avenues to cell biological studies of calpain function and eventually may alleviate pathological states caused by calpain malfunction. |
DOI | 10.1074/jbc.C100700200 |
Alternate Journal | J. Biol. Chem. |
PubMed ID | 11809743 |
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