Calpains are intracellular cysteine endopeptidases that combine protease activity with a dependence on Ca2+ binding. Here we describe the conformational changes leading to the calpain activation, occurring in the enzyme purified from human erythrocytes, studied in solution using small angle X-ray scattering (SAXS). Addition of Ca2+ determines the formation of large soluble aggregates that can be dissociated either chelating these ions or adding cahotropic salts in solution. On the other side, our SAXS studies revealed that the addition of Ca2+ in the presence of inhibitors as E64 or leupeptin triggers a reversible conformational transition leading to a proper assembly of the active site without any aggregation or dissociation process. It is suggested that the observed conformational changes can be considered as the early step in the sequence of molecular events leading to calpain activation.
|Number of pages||9|
|Publication status||Published - 2004|
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