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
Date Published2002 Mar 15
KeywordsAmino Acid Sequence, Animals, Calcium, Calcium-Binding Proteins, Calpain, Enzyme Activation, Humans, Molecular Sequence Data, Peptide Fragments, Rats

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.

Alternate JournalJ. Biol. Chem.
PubMed ID11809743