Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex

• DOI: 10.1038/s41467-017-01497-1
• Publication Date: 2017-10-30T14:06:55Z
• Authors: Michal T. Boniecki; Sven A. Freibert; Ulrich Mühlenhoff; Roland Lill; Miroslaw Cygler
• Keywords: Iron–sulfur cluster; Frataxin

Iron-sulfur (Fe/S) clusters are essential protein cofactors crucial for many cellular functions including DNA maintenance, translation, and energy conversion. De novo Fe/S cluster synthesis occurs on the mitochondrial scaffold ISCU requires cysteine desulfurase NFS1, ferredoxin, frataxin, small factors ISD11 ACP (acyl carrier protein). Both mechanism of function ISD11-ACP poorly understood. Here, we present crystal structures three different NFS1-ISD11-ACP complexes with without ISCU, use SAXS analyses to define 3D architecture complete biosynthetic complex. Our structural biochemical studies provide mechanistic insights into at catalytic center defined by active-site Cys NFS1 conserved Cys, Asp, His residues ISCU. We assign specific regulatory rather than roles that link lipid status.