Histidine ligands in bacterial metallothionein enhance cluster stability
Histidine ligands in bacterial metallothionein enhance cluster stability
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DOI：
10.1007/s00775-006-0196-4
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发表时间：
2007-03-01
影响因子：
3
通讯作者：
Sadler, Peter J.
中科院分区：
文献类型：
--
作者：
Blindauer, Claudia A.;Razi, M. Tahir;Sadler, Peter J.
蓝藻金属硫蛋白（MT） SmtA是细菌MT的原型，并防止锌水平升高。与哺乳动物的mt相反，细菌的mt不仅通过半胱氨酸硫与金属离子配合，而且还通过组氨酸氮与金属离子配合。为了研究组氨酸在这些金属硫簇中的配位是否比仅s配位更有优势，我们将蓝细菌MT SmtA中的两个金属结合组氨酸残基从聚球菌PCC7942突变为半胱氨酸。我们发现突变蛋白仍然能够结合多达四个锌离子，就像野生型蛋白一样。然而，突变扰乱了蛋白质折叠和金属结合动力学。有趣的是，SmtA的几个同源物也显示出这两个残基的变化。我们得出结论，聚球菌PCC7942 SmtA中的组氨酸残基具有稳定作用，这是由于静电相互作用影响蛋白质折叠和金属簇电荷，并参与微调结合金属离子的反应性。
The cyanobacterial metallothionein (MT) SmtA is the prototype for bacterial MTs and protects against elevated levels of zinc. In contrast to mammalian MTs, bacterial MTs coordinate to metal ions not only via cysteine sulfurs, but unusually for MTs, also via histidine nitrogens. To investigate whether histidine coordination in these metal-sulfur clusters provides advantages over S-coordination only, we mutated the two metal-binding histidine residues in the cyanobacterial MT SmtA from Synechococcus PCC7942 to cysteines. We show that the mutant proteins are still capable of binding up to four zinc ions as is the wild-type protein. However, the mutations perturb protein folding and metal-binding dynamics. Interestingly, several homologues of SmtA also show variations in these two residues. We conclude that histidine residues in Synechococcus PCC7942 SmtA have a stabilising effect due to electrostatic interactions that impact on protein folding and metal cluster charge, and are involved in fine-tuning the reactivity of the bound metal ions.