Abstract
Calpains, the cytoplasmic Ca2+-activated regulatory proteases, have no simple and clearly definable cleavage site specificity, which is in sharp contrast to digestive (e.g., pancreatic) proteases. For calpains, an approximate 10-aa segment having a variety of sequences and spanning the scissile bond, governs proteolytic cleavage. This permissivity is a precondition for calpains to act on several different substrate proteins in the cell. The specificity of calpain action may be ensured by anchoring/targeting proteins. Intriguingly, the established endogenous inhibitor protein, calpastatin, might also serve as a storage site. Furthermore, specificity may be encoded in the ‘goodness’ of the undecapeptide sequence in substrate proteins. Novel approaches are needed to reveal how calpains find their substrates in cells at the proper time and location.
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