title: Crystal structure of calcium-free human sorcin: a member of the penta-EF-hand protein family.
abstract: Sorcin is a 22 kD calcium-binding protein that is found in a wide variety of 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 motifs 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 A resolution. Apart from an extended N-terminal portion, the sorcin molecule has a globular shape. The C-terminal domain is predominantly alpha-helical, containing eight alpha-helices and connecting loops incorporating five EF hands. Sorcin forms dimers through the association of the unpaired EF5, confirming this as the mode of association in the dimerization of PEF proteins. Comparison with calpain dVI reveals that the general folds of the individual EF-hand motifs are conserved, especially that of EF1, the novel EF-hand motif characteristic of the family. Detailed structural comparisons of sorcin with other members 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 calcium-induced conformational change may be modest and localized within this pair of EF-hands. Overall, the results derived from the structural observations support the view that, in sorcin, calcium signaling takes place through the first pair of EF-hands.
authors.affiliation: Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139-4211, USA. xiaoling_xie@vpharm.com
authors.forename: X
authors.initials: X
authors.lastname: Xie
authors.forename: M D
authors.initials: MD
authors.lastname: Dwyer
authors.forename: L
authors.initials: L
authors.lastname: Swenson
authors.forename: M H
authors.initials: MH
authors.lastname: Parker
authors.forename: M C
authors.initials: MC
authors.lastname: Botfield
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017302:Annexins / Q000737:chemistry; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D002154:Calpain / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D020832:EF Hand Motifs; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D017302:Annexins; D002135:Calcium-Binding Proteins; C503113:SRI protein, human; D002154:Calpain