Iron−Sulfur Cluster Biosynthesis: Characterization of a Molten Globule Domain in Human NFU

Yushi Liu, J. A. Cowan
2009 Biochemistry  
Human NFU (also known as HIRIP5) has been implicated in cellular iron-sulfur cluster biosynthesis. Bacterial and yeast forms are smaller than the human protein and are homologous to the C-terminal domain of human NFU. This C-terminal domain contains a pair of redox active cysteines and demonstrates thioredoxin-like activity by both binding to and mediating persulfide bond cleavage of sulfur-loaded IscS; the sulfide donor for [2Fe-2S] cluster assembly on ISU-type scaffold proteins. Herein, human
more » ... NFU is shown to possess a novel combination of a molten-globule type C-terminal domain and an N-terminal domain with a fully-folded regular tertiary structure. The molten globule characteristics of the C-terminal domain have been evaluated by ANS binding, the kinetics of trypsin digestion, and HSQC NMR studies. Human NFU is a functionally competent reducing agent for cysteinyl persulfide bond cleavage, releasing inorganic sulfide for incorporation into the ISU-bound [2Fe-2S] cluster, a reactivity that might be facilitated by the flexibility of the C-terminal domain.
doi:10.1021/bi9002524 pmid:19722697 pmcid:PMC2766508 fatcat:gcanxm7dp5eplcp2atnzuuauzy