ISCU Protein, Human (sf9, His)

ISCU, a pivotal mitochondrial scaffold protein within the core iron-sulfur cluster (ISC) assembly complex, serves as the structural foundation for the assembly of [2Fe-2S] clusters. In the intricate process of de novo synthesis of [2Fe-2S] clusters, initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1), ISCU plays a central role by receiving persulfide in a FXN-dependent manner. Stabilization of this complex is facilitated by FDX2, providing reducing equivalents for efficient [2Fe-2S] cluster assembly. Subsequently, ISCU acts as a crucial intermediary, transferring the assembled [2Fe-2S] cluster to chaperone proteins, including HSCB, HSPA9, and GLRX5. Notably, ISCU exhibits dynamic conformational states, alternating between structured (S) and disordered (D) forms. Its zinc-dependent modulation of NFS1 desulfurase activity and influence on the interaction between FXN and the cysteine desulfurase complex further underscore its multifaceted role. Additionally, as a cytoplasmic scaffold protein, ISCU contributes to the structural framework of the cytoplasmic ISC assembly complex, participating in the assembly of Fe-S clusters and potentially contributing to cytoplasmic iron-sulfur protein biogenesis.