Crystal structure of calcium-free human sorcin: A member of the penta-EF-hand protein family

Sorcin is a 22 kD calcium-binding protein that is found in a wide variety o f cell types, such as heart, muscle, brain and adrenal medulla. It belongs to the penta-EF-hand (PEF) protein family, which contains five EF-hand moti fs that associate with membranes in a calcium-dependent manner. Prototypic members of this family are the calcium-binding domains of calpain, such as calpain dVI. Full-length human sorcin has been crystallized in the absence of calcium and the structure determined at 2.2 Angstrom resolution. Apart f rom an extended N-terminal portion, the sorcin molecule has a globular shap e. The C-terminal domain is predominantly alpha -helical, containing eight alpha -helices and connecting loops incorporating five EF hands. Sorcin for ms dimers through the association of the Impaired EF5, confirming this as t he mode of association in the dimerization of PEF proteins. Comparison with calpain dVI reveals that the general folds of the individual EF-hand motif s are conserved, especially that of EF1, the novel EF-hand motif characteri stic of the family. Detailed structural comparisons of sorcin with other me mbers of PEF indicate that the EF-hand pair EF1-EF2 is likely to correspond to the two physiologically relevant calcium-binding sites and that the cal cium-induced conformational change may be modest and localized within this pair of EF-hands. Overall, the results derived from the structural observat ions support the view that, in sorcin, calcium signaling takes place throug h the first pair of EF-hands.