Human anamorsin binds [2Fe-2S] clusters with unique electronic properties
Human anamorsin binds [2Fe-2S] clusters with unique electronic properties
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DOI：
10.1007/s00775-013-1033-1
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发表时间：
2013-12-01
影响因子：
3
通讯作者：
Pandelia, Maria-Eirini
中科院分区：
文献类型：
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作者：
Banci, Lucia;Ciofi-Baffoni, Simone;Pandelia, Maria-Eirini
真核anamorsin蛋白家族，最近已被提出为在胞质铁硫（Fe/S）蛋白生物发生的早期步骤中起作用的电子传递链的一部分，其特征在于包含两个保守的富含半胱氨酸的基序（CX 8 CX 2CXC和CX 2CX 7 CX 2C）的大部分非结构化结构域（CIAPIN 1），其Fe/S结合特性和电子结构未被很好地定义。在这里，我们发现（1）人anamorsin中的每个基序能够通过其四个半胱氨酸残基独立地结合[2Fe-2S]簇，一个簇的结合相互排斥第二个簇的结合，（2）还原的[2Fe-2S]（+）簇在其配位环境中表现出独特的电子结构，具有相当大的各向异性，不同于还原的[2Fe-2S]（+）簇中观察到的，植物型和脊椎动物型[2Fe-2S]铁氧还蛋白中心，（3）与CX 2CX 7 CX 2C基序结合的还原簇揭示了前所未有的价定位到离域转变作为温度的函数，和（4）只有与CX 8 CX 2CX C基序结合的[2Fe-2S]簇参与与其生理蛋白伴侣Ndor 1的电子转移。两个[2Fe-2S]中心的独特电子性质可以通过考虑两个富含半胱氨酸的基序都位于高度非结构化和灵活的蛋白质区域来解释，其局部构象异质性可以诱导金属配位的各向异性。这项研究有助于理解的CIAPIN 1域的功能作用的anamorsin家族，这表明，只有[2Fe-2S]簇结合到CX 8 CX 2CXC基序是必不可少的电子转移链组装胞质Fe/S蛋白。
The eukaryotic anamorsin protein family, which has recently been proposed to be part of an electron transfer chain functioning in the early steps of cytosolic iron-sulfur (Fe/S) protein biogenesis, is characterized by a largely unstructured domain (CIAPIN1) containing two conserved cysteine-rich motifs (CX8CX2CXC and CX2CX7CX2C) whose Fe/S binding properties and electronic structures are not well defined. Here, we found that (1) each motif in human anamorsin is able to bind independently a [2Fe-2S] cluster through its four cysteine residues, the binding of one cluster mutually excluding the binding of the second, (2) the reduced [2Fe-2S](+) clusters exhibit a unique electronic structure with considerable anisotropy in their coordination environment, different from that observed in reduced, plant-type and vertebrate-type [2Fe-2S] ferredoxin centers, (3) the reduced cluster bound to the CX2CX7CX2C motif reveals an unprecedented valence localization-to-delocalization transition as a function of temperature, and (4) only the [2Fe-2S] cluster bound to the CX8CX2CXC motif is involved in the electron transfer with its physiological protein partner Ndor1. The unique electronic properties of both [2Fe-2S] centers can be interpreted by considering that both cysteine-rich motifs are located in a highly unstructured and flexible protein region, whose local conformational heterogeneity can induce anisotropy in metal coordination. This study contributes to the understanding of the functional role of the CIAPIN1 domain in the anamorsin family, suggesting that only the [2Fe-2S] cluster bound to the CX8CX2CXC motif is indispensable in the electron transfer chain assembling cytosolic Fe/S proteins.