Magnetic Resonance Center (CERM), University of Florence and Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (CIRMMP), Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Magnetic Resonance Center (CERM), University of Florence and Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (CIRMMP), Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy; Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.
Biochim Biophys Acta Gen Subj. 2018 Sep;1862(9):1980-1987. doi: 10.1016/j.bbagen.2018.05.019. Epub 2018 May 26.
The CIA2A protein, in complex with CIAO1, has been proposed to be exclusively implicated in the maturation of cytosolic aconitase. However, how the CIA2A-CIAO1 complex generates active aconitase is still unknown and the available structural information has not provided any crucial insights into the molecular function of CIA2A.
In this work we have characterized the Fe/S cluster binding properties of CIA2A and of the CIA2A-CIAO1 complex via NMR, UV - vis absorption and EPR spectroscopies and we have investigated how the Fe/S cluster is transferred to inactive aconitase/IRP1 protein.
We found that an heterotrimeric species formed by two molecules of CIA2A and one of CIAO1 can bind one [4Fe-4S] cluster and that residue Cys90 of CIA2A is one of the cluster ligand. The holo trimeric complex is able to transfer the [4Fe-4S] cluster to apo-IRP1 thus generating the active form of aconitase.
These findings, which highlight a functional role for CIA2A-CIAO1 complex in aconitase maturation, raises a broad interest and can have a high impact on the community studying metal trafficking and iron‑sulfur protein biogenesis. The present study can provide solid bases for further investigation of the molecular mechanisms involving also other CIA machinery proteins.
CIA2A 蛋白与 CIAO1 形成复合物，被认为专门参与细胞质 aconitase 的成熟。然而，CIA2A-CIAO1 复合物如何产生活性 aconitase 仍不清楚，并且现有结构信息并未为 CIA2A 的分子功能提供任何关键见解。
在这项工作中，我们通过 NMR、UV-vis 吸收和 EPR 光谱学表征了 CIA2A 和 CIA2A-CIAO1 复合物的 Fe/S 簇结合特性，并研究了 Fe/S 簇如何转移到无活性 aconitase/IRP1 蛋白。
我们发现由两个 CIA2A 分子和一个 CIAO1 分子形成的异三聚体可以结合一个 [4Fe-4S]簇，并且 CIA2A 的残基 Cys90 是簇配体之一。全同三聚体复合物能够将 [4Fe-4S]簇转移到 apo-IRP1 上，从而生成活性 aconitase。
这些发现强调了 CIA2A-CIAO1 复合物在 aconitase 成熟中的功能作用，引起了广泛的兴趣，并可能对研究金属转运和铁硫蛋白生物发生的社区产生重大影响。本研究为进一步研究涉及其他 CIA 机械蛋白的分子机制提供了坚实的基础。
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