The CIA Targeting Complex Is Highly Regulated and Provides Two Distinct Binding Sites for Client Iron-Sulfur Proteins.
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.
Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Diana C
DC
Odermatt
Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland. Electronic address: gari@imcr.uzh.ch.
Kerstin
K
Gari
D001665:Binding Sites / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D056511:Metallochaperones / Q000378:metabolism; D008667:Metalloproteins; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D013455:Sulfur / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C112111:CIAO1 protein, human; C569498:CIAO2B protein, human; D002352:Carrier Proteins; D007506:Iron-Sulfur Proteins; C416322:MMS19 protein, human; D056511:Metallochaperones; D008667:Metalloproteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D013455:Sulfur; D007501:Iron; D004265:DNA Helicases
CIA machinery; CIAO1; DNA repair; DNA replication; MIP18; MMS19; XPD; iron-sulfur cluster