Calpastatin subdomains A and C are activators of calpain.

TitleCalpastatin subdomains A and C are activators of calpain.
Publication TypeJournal Article
Year of Publication2002
AuthorsTompa, P., Z. Mucsi, G. Orosz, and P. Friedrich
JournalJ Biol Chem
Volume277
Issue11
Pagination9022-6
Date Published2002 Mar 15
ISSN0021-9258
KeywordsAmino 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.

DOI10.1074/jbc.C100700200
Alternate JournalJ. Biol. Chem.
PubMed ID11809743