Abstract
Iron-sulfur (Fe-S) clusters, the ubiquitous protein cofactors found in all kingdoms of life, perform a myriad of functions including nitrogen fixation, ribosome assembly, DNA repair, mitochondrial respiration, and metabolite catabolism. The biogenesis of Fe-S clusters is a multi-step process that involves the participation of many protein partners. Recent biophysical studies, involving X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and small angle X-ray scattering (SAXS), have greatly improved our understanding of these steps. In this review, after describing the biological importance of iron sulfur proteins, we focus on the contributions of NMR spectroscopy has made to our understanding of the structures, dynamics, and interactions of proteins involved in the biosynthesis of Fe-S cluster proteins.
Highlights
Metal ions are essential to life and, to function, almost half of all enzymes must associate with one or more particular metal ions [1,2]
After describing the biological importance of iron sulfur proteins, we focus on the contributions of nuclear magnetic resonance (NMR) spectroscopy has made to our understanding of the structures, dynamics, and interactions of proteins involved in the biosynthesis of Fe-S cluster proteins
We demonstrated that E. coli Acp substitutes for human mitochondrial acyl carrier protein (ACP) in the cysteine desulfurase complex produced by co-expressing human NFS1 and ISD11 in E. coli cells and determined its stoichiometry stoichiometry to be [NFS1]2:[ISD11]2:[Acp]2 [117], abbreviated as (NIA)2
Summary
Metal ions are essential to life and, to function, almost half of all enzymes must associate with one or more particular metal ions [1,2]. The first step is de novo assembly of a nascent [2Fe-2S] cluster on the scaffold protein ISCU through coordinated reactions involving a set of essential ISC proteins: the cysteine desulfurase (NFS1), an accessory protein (ISD11), the mitochondrial acyl carrier protein (ACP), ferredoxin (FDX1/2), and frataxin (FXN) [24,35,36,37]. The [2Fe-2S] clusters can be subsequently transferred to target proteins, trafficked to late acting protein complexes to form [4Fe-4S] clusters, or exported from mitochondria as a sulfur-containing species used in the cytosolic iron-sulfur assembly (CIA) machinery [40,41,42]. The assembled [2Fe-2S] cluster is transferred from ISCU to proteins (e.g., Rieske protein), used for synthesis of a sulfur-containing species (X-S) for cytosolic Fea monothiolS glutaredoxin assisted by the of dedicated chaperone–cochaperone (HSP70-HSC20). Because much of our understanding of these human machineries stems from studies of the bacterial and yeast ISC and CIA machineries, these systems are briefly mentioned
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