Imai Fabiana Lica, Nagata Koji, Yonezawa Naoto, Nakano Minoru, Tanokura Masaru
Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Feb 1;64(Pt 2):70-6. doi: 10.1107/S1744309107068236. Epub 2008 Jan 31.
S100A13 is a member of the S100 family of EF-hand-containing calcium-binding proteins. S100A13 plays an important role in the secretion of fibroblast growth factor-1 and interleukin 1 alpha, two pro-angiogenic factors released by the nonclassical endoplasmic reticulum/Golgi-independent secretory pathway. The X-ray crystal structure of human S100A13 at pH 7.5 was determined at 1.8 A resolution. The structure was solved by molecular replacement and was refined to a final R factor of 19.0%. The structure revealed that human S100A13 exists as a homodimer with two calcium ions bound to each protomer. The protomer is composed of four alpha-helices (alpha(1)-alpha(4)), which form a pair of EF-hand motifs. Dimerization occurs by hydrophobic interactions between helices alpha(1) and alpha(4) and by intermolecular hydrogen bonds between residues from helix alpha(1) and the residues between alpha(2) and alpha(3) of both chains. Despite the high similarity of the backbone conformation in each protomer, the crystal structures of human S100A13 at pH 7.5 (this study) and at pH 6.0 [Li et al. (2007), Biochem. Biophys. Res. Commun. 356, 616-621] exhibit recognizable differences in the relative orientation ( approximately 2.5 degrees) of the protomers within the dimer and also remarkable differences in the side-chain conformations of several amino-acid residues.
S100A13是含EF手型结构的钙结合蛋白S100家族的成员之一。S100A13在成纤维细胞生长因子-1和白细胞介素1α的分泌过程中发挥重要作用，这两种促血管生成因子通过非经典的不依赖内质网/高尔基体的分泌途径释放。人类S100A13在pH 7.5时的X射线晶体结构在1.8 Å分辨率下得以确定。该结构通过分子置换法解析，最终精修后的R因子为19.0%。结构显示，人类S100A13以同型二聚体形式存在，每个亚基结合有两个钙离子。亚基由四个α螺旋（α(1)-α(4)）组成，形成一对EF手型基序。二聚化通过α(1)和α(4)螺旋之间的疏水相互作用以及α(1)螺旋上的残基与两条链的α(2)和α(3)之间的残基形成的分子间氢键实现。尽管每个亚基的主链构象高度相似，但人类S100A13在pH 7.5（本研究）和pH 6.0时的晶体结构[Li等人（2007年），《生物化学与生物物理研究通讯》356，616 - 621]在二聚体内亚基的相对取向（约2.5°）上呈现出可识别的差异，并且在几个氨基酸残基的侧链构象上也存在显著差异。
