Sillen Alain, Verheyden Stefan, Delfosse Lotte, Braem Tania, Robben Johan, Volckaert Guido, Engelborghs Yves
Laboratory of Biomolecular Dynamics, Catholic University of Leuven, Belgium.
Biophys J. 2003 Sep;85(3):1882-93. doi: 10.1016/S0006-3495(03)74616-5.
The calcium-binding protein isolated from the sarcoplasm of the muscles of the sand worm Nereis diversicolor has four EF-hands and three active binding sites for Ca(2+) or Mg(2+). Nereis diversicolor sarcoplasmic calcium-binding protein contains three tryptophan residues at positions 4, 57, and 170, respectively. The Wt protein shows a very limited fluorescence increase upon binding of Ca(2+) or Mg(2+). Single-tryptophan-containing mutants were produced and purified. The fluorescence titrations of these mutants show a limited decrease of the affinity for calcium, but no alterations of the cooperativity. Upon adding calcium, Trp170 shows a strong fluorescence increase, Trp57 an extensive fluorescence decrease, and Trp4 shows no fluorescence change. Therefore mutant W4F/W170F is ideally suited to analyze the fluorescence titrations and to study the binding mechanism. Mutations of the calcium ligands at the z-position in the three binding sites show no effect at site I and a total loss of cooperativity at sites III and IV. The quenching of Trp57 upon calcium binding is dependent on the presence of arginine R25, but this residue is not just a simple dynamic quencher. The role of the salt bridge R25-D58 is also investigated.
从多毛纲沙蚕肌肉肌浆中分离出的钙结合蛋白有四个EF手结构域和三个结合Ca(2+)或Mg(2+)的活性位点。多毛纲沙蚕肌浆钙结合蛋白在第4、57和170位分别含有三个色氨酸残基。野生型蛋白在结合Ca(2+)或Mg(2+)时荧光增强非常有限。制备并纯化了含单个色氨酸的突变体。这些突变体的荧光滴定显示对钙的亲和力有有限降低,但协同性没有改变。加入钙后,Trp170荧光强烈增强,Trp57荧光大幅降低,Trp4荧光无变化。因此,突变体W4F/W170F非常适合分析荧光滴定并研究结合机制。三个结合位点z位置的钙配体突变在I位点无影响,在III和IV位点协同性完全丧失。钙结合时Trp57的淬灭依赖于精氨酸R25的存在,但该残基不只是一个简单的动态淬灭剂。还研究了盐桥R25-D58的作用。