Xie X, Dwyer M D, Swenson L, Parker M H, Botfield M C
Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139-4211, USA.
Protein Sci. 2001 Dec;10(12):2419-25. doi: 10.1110/ps.36701.
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.
索辛蛋白是一种22kD的钙结合蛋白，存在于多种细胞类型中，如心脏、肌肉、大脑和肾上腺髓质。它属于五聚EF手（PEF）蛋白家族，该家族包含五个EF手基序，它们以钙依赖的方式与膜结合。该家族的典型成员是钙蛋白酶的钙结合结构域，如钙蛋白酶dVI。全长人索辛蛋白已在无钙条件下结晶，并以2.2埃的分辨率确定了其结构。除了延伸的N端部分外，索辛蛋白分子呈球状。C端结构域主要是α螺旋结构，包含八个α螺旋和连接环，其中包含五个EF手。索辛蛋白通过未配对的EF5的结合形成二聚体，证实这是PEF蛋白二聚化的结合模式。与钙蛋白酶dVI的比较表明，各个EF手基序的总体折叠是保守的，尤其是EF1的折叠，它是该家族特有的新型EF手基序。索辛蛋白与PEF其他成员的详细结构比较表明，EF手对EF1-EF2可能对应于两个生理相关的钙结合位点，并且钙诱导的构象变化可能较小且局限于这对EF手中。总体而言，从结构观察中得出的结果支持这样一种观点，即在索辛蛋白中，钙信号传导是通过第一对EF手发生的。
