CIA Targeting Complex transfers 4Fe-4S cluster to apoproteins
Species Homo sapiens
A complex of four proteins termed CIA targeting complex is involved in the delivery of the NUBP1-NUBP2-bound Fe/S cluster to specific target apoproteins. NARFL (IOP1, Nar1 in yeast) is similar in sequence to iron-only hydrogenases and binds two [4Fe-4S] clusters. These cofactors are essential for biogenesis but their molecular function is unknown. The WD40 domain protein CIAO1 (Cia1 in yeast) forms a propeller-like structure which may serve as a docking site for the other members of the CIA targeting complex. The role of FAM96B (YHR122W, CIA2 in yeast) and MMS19 is still unclear, but they show some specificity for the delivery of Fe/S clusters into certain target apoproteins. They directly interact with numerous Fe/S target proteins including many proteins involved in nuclear DNA integrity and maintenance such as DNA polymerases (POLD1), helicases of the DNA repair pathway (XPD or FANCJ) or of telomere maintenance (RTEL1), and primases. Cells with mutated MMS19 are hypersensitive to DNA damage and have elongated telomeres therefore these target proteins are relevant to various cancer-related diseases and aging.
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