The asymmetric IscA homodimer with an exposed [2Fe-2S] cluster suggests the structural basis of the fe-S cluster biosynthetic scaffold
The asymmetric IscA homodimer with an exposed [2Fe-2S] cluster suggests the structural basis of the fe-S cluster biosynthetic scaffold
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DOI：
10.1016/j.jmb.2006.04.067
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发表时间：
2006-06-30
影响因子：
5.6
通讯作者：
Nakai, Masato
中科院分区：
文献类型：
--
作者：
Morimoto, Kozo;Yamashita, Eiki;Nakai, Masato
研究表明，所谓的支架蛋白通过为Fe-S簇的组装提供中间位点而在Fe-S簇的生物合成中是至关重要的。然而，由于没有关于具有结合的Fe-S簇中间体的这种支架蛋白的结构信息，因此Fe-S簇生物合成的核心的结构基础仍然知之甚少。在这里，我们报告的第一个Fe-S簇结合的支架蛋白，IscA，从细长热聚球藻，它携带三个严格保守的半胱氨酸残基的晶体结构。令人惊讶的是，一个部分暴露的[2 Fe-2S]簇与两个构象不同的IscA原聚体（称为α和β）配位，其中α通过Cys 37、Cys 101、Cys 103进行不对称半胱氨酰连接，β通过Cys 103进行不对称半胱氨酰连接。在晶体中，两个α β二聚体通过β原聚体的中心结构域形成不寻常的结构域交换的四聚体。再加上额外的生化数据支持其生理相关的配置，我们提出，独特的不对称Fe-S簇的协调和由此产生的，不同的构象稳定性的两个IscA的原聚体的IscA型Fe-S簇的生物合成支架的功能的核心。(c)2006爱思唯尔有限公司版权所有。
It has been shown that the so-called scaffold proteins are vital in Fe-S cluster biosynthesis by providing an intermediate site for the assembly of Fe-S clusters. However, since no structural information on such scaffold proteins with bound Fe-S cluster intermediates is available, the structural basis of the core of Fe-S Cluster biosynthesis remains poorly understood. Here we report the first Fe-S cluster-bound crystal structure of a scaffold protein, IscA, from Thermosynechococcus elongatus, which carries three strictly conserved cysteine residues. Surprisingly, one partially exposed [2Fe-2S] cluster is coordinated by two conformationally distinct IscA protomers, termed alpha and beta, with asymmetric cysteinyl ligation by Cys37, Cys101, Cys103 from alpha and Cys103 from beta. In the crystal, two alpha beta dimers form an unusual domain-swapped tetramer via central domains of beta protomers. Together with additional biochemical data supporting its physiologically relevant configuration, we propose that the unique asymmetric Fe-S cluster coordination and the resulting, distinct conformational stabilities of the two IscA protomers are central to the function of IscA-type Fe-S cluster biosynthetic scaffold. (c) 2006 Elsevier Ltd. All rights reserved.