Odermatt Diana C, Gari Kerstin
Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Cell Rep. 2017 Feb 7;18(6):1434-1443. doi: 10.1016/j.celrep.2017.01.037.
The cytoplasmic iron-sulfur assembly (CIA) targeting complex is required for the transfer of an iron-sulfur (Fe-S) cluster to cytoplasmic and nuclear proteins, but how it engages with client proteins is unknown. Here, we show that the complex members MIP18 and CIAO1 associate with the C terminus of MMS19. By doing so, they form a docking site for Fe-S proteins that is disrupted in the absence of either MMS19 or MIP18. The Fe-S helicase XPD seems to be the only exception, since it can interact with MMS19 independently of MIP18 and CIAO1. We further show that the direct interaction between MMS19 and MIP18 is required to protect MIP18 from proteasomal degradation. Taken together, these data suggest a remarkably regulated interaction between the CIA targeting complex and client proteins and raise the possibility that Fe-S cluster transfer is controlled, at least in part, by the stability of the CIA targeting complex itself.
胞质铁硫组装（CIA）靶向复合物是将铁硫（Fe-S）簇转移至胞质和核蛋白所必需的，但它如何与客户蛋白结合尚不清楚。在此，我们表明复合物成员MIP18和CIAO1与MMS19的C末端相关联。通过这样做，它们形成了一个Fe-S蛋白的对接位点，在没有MMS19或MIP18的情况下该位点会被破坏。Fe-S解旋酶XPD似乎是唯一的例外，因为它可以独立于MIP18和CIAO1与MMS19相互作用。我们进一步表明，MMS19和MIP18之间的直接相互作用对于保护MIP18免受蛋白酶体降解是必需的。综上所述，这些数据表明CIA靶向复合物与客户蛋白之间存在显著调节的相互作用，并增加了Fe-S簇转移至少部分受CIA靶向复合物自身稳定性控制的可能性。
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