ISCU interacts with NFU1, and ISCU[4Fe-4S] transfers its Fe-S cluster to NFU1 leading to the production of holo-NFU1.

ABSTRACT: NFU1 is a late-acting factor in the biogenesis of human mitochondrial iron-sulfur proteins. Mutations in NFU1 are associated with genetic diseases such as multiple mitochondrial dysfunctions syndrome 1 (MMDS1) that involve defects in mitochondrial [4Fe-4S] proteins. We present results from NMR spectroscopy, small angle X-ray scattering, size exclusion chromatography, and isothermal titration calorimetry showing that the structured conformer of human ISCU binds human NFU1. The dissociation constant determined by ITC is K_d = 1.1 ± 0.2 μM. NMR and SAXS studies led to a structural model for the complex in which the cluster binding region of ISCU interacts with two α-helices in the C-terminal domain of NFU1. In vitro experiments demonstrate that ISCU[4Fe-4S] transfers its Fe-S cluste

SUBMITTER: Cai K 

PROVIDER: S-EPMC7261492 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature