Iron loading site on the Fe-S cluster assembly scaffold protein is distinct from the active site

Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Andria V RodriguesTimothy L Stemmler

Abstract

Iron-sulfur (Fe-S) cluster containing proteins are utilized in almost every biochemical pathway. The unique redox and coordination chemistry associated with the cofactor allows these proteins to participate in a diverse set of reactions, including electron transfer, enzyme catalysis, DNA synthesis and signaling within several pathways. Due to the high reactivity of the metal, it is not surprising that biological Fe-S cluster assembly is tightly regulated within cells. In yeast, the major assembly pathway for Fe-S clusters is the mitochondrial ISC pathway. Yeast Fe-S cluster assembly is accomplished using the scaffold protein (Isu1) as the molecular foundation, with assistance from the cysteine desulfurase (Nfs1) to provide sulfur, the accessory protein (Isd11) to regulate Nfs1 activity, the yeast frataxin homologue (Yfh1) to regulate Nfs1 activity and participate in Isu1 Fe loading possibly as a chaperone, and the ferredoxin (Yah1) to provide reducing equivalents for assembly. In this report, we utilize calorimetric and spectroscopic methods to provide molecular insight into how wt-Isu1 from S. cerevisiae becomes loaded with iron. Isothermal titration calorimetry and an iron competition binding assay were developed to character...Continue Reading

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Citations

Oct 8, 2016·Metallomics : Integrated Biometal Science·N Maio, T A Rouault
Oct 28, 2016·Metallomics : Integrated Biometal Science·Stephen P DzulTimothy L Stemmler
Sep 19, 2019·ELife·Ma Teresa Pellicer MartinezNick E Le Brun
Sep 19, 2019·Metallomics : Integrated Biometal Science·Brianne E LewisTimothy L Stemmler
Sep 25, 2017·Mitochondrion·Agostinho G RochaAndrew Dancis
Jul 3, 2021·International Journal of Molecular Sciences·Courtney J CampbellTimothy L Stemmler
Sep 25, 2017·Environmental Science & Technology·Shashank S PawitwarMasafumi Yoshinaga

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