Calpastatin subdomains A and C are activators of calpain

Peter Tompa, Zoltán Mucsi, György Orosz, Peter Friedrich

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 Ca2+-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 μ-calpain and rat m-calpain. The two peptides significantly activate both calpains: the Ca2+ concentration required for half-maximal activity is lowered from 4.3 to 2.4 μ,M for μ-calpain and from 250 to 140 μM for m-calpain. The EC50 concentration of the peptides is 7.5 μM for μ-calpain and 25 μM for m-calpain. It is noteworthy that at low Ca2+ concentrations (1-2 μM for μ-calpain and 70-110 μM 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.

Original languageEnglish
Pages (from-to)9022-9026
Number of pages5
JournalJournal of Biological Chemistry
Volume277
Issue number11
DOIs
Publication statusPublished - Mar 15 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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