A Molecular Mechanism for Copper Transportation to Tyrosinase That Is Assisted by a Metallochaperone, Caddie Protein
A Molecular Mechanism for Copper Transportation to Tyrosinase That Is Assisted by a Metallochaperone, Caddie Protein
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DOI：
10.1074/jbc.m111.256818
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发表时间：
2011-08-26
影响因子：
4.8
通讯作者：
Sugiyama, Masanori
中科院分区：
文献类型：
--
作者：
Matoba, Yasuyuki;Bando, Naohiko;Sugiyama, Masanori
酪氨酸酶的 Cu(II) 浸泡晶体结构存在于与蛋白质的复合物中，称为“球童”，我们之前确定其催化中心有两个铜离子。我们在球童蛋白中鉴定了两个铜结合位点，并推测与球童结合的铜可能被转运到酪氨酸酶催化中心。在我们目前的研究中，在1.16-1.58埃的分辨率下，我们确定了通过改变铜离子的浸泡时间制备的与球童复合的酪氨酸酶的晶体结构，以及与不同球童突变体复合的酪氨酸酶的结构，这些突变体表现出很少或没有激活酪氨酸酶的能力。基于这些结构，我们提出了一种分子机制，在球童作为金属伴侣的帮助下，两个铜离子被转运到酪氨酸酶催化中心。
The Cu(II)-soaked crystal structure of tyrosinase that is present in a complex with a protein, designated "caddie," which we previously determined, possesses two copper ions at its catalytic center. We had identified two copper-binding sites in the caddie protein and speculated that copper bound to caddie may be transported to the tyrosinase catalytic center. In our present study, at a 1.16-1.58 angstrom resolution, we determined the crystal structures of tyrosinase complexed with caddie prepared by altering the soaking time of the copper ion and the structures of tyrosinase complexed with different caddie mutants that display little or no capacity to activate tyrosinase. Based on these structures, we propose a molecular mechanism by which two copper ions are transported to the tyrosinase catalytic center with the assistance of caddie acting as a metallochaperone.