5T0V

Architecture of the Yeast Mitochondrial Iron-Sulfur Cluster Assembly Machinery: the Sub-Complex Formed by the Iron Donor, Yfh1, and the Scaffold, Isu1

Summary for 5T0V

• Entry DOI: 10.2210/pdb5t0v/pdb
• Related: 5KZ5
• EMDB information: 8301 8341
• Descriptor: Iron sulfur cluster assembly protein 1, mitochondrial, Frataxin homolog, mitochondrial (2 entities in total)
• Functional Keywords: friedreich ataxia, frataxin, iron-sulfur protein, mitochondria, protein complex, oxidoreductase
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Total number of polymer chains: 48
• Total formula weight: 692156.35

Authors

Ranatunga, W.,Gakh, O.,Galeano, B.K.,Smith IV, D.Y.,Soderberg, C.A.,Al-Karadaghi, S.,Thompson, J.R.,Isaya, G. (deposition date: 2016-08-16, release date: 2016-08-31, Last modification date: 2024-10-09)

Primary citation

Ranatunga, W.,Gakh, O.,Galeano, B.K.,Smith IV, D.Y.,Soderberg, C.A.,Al-Karadaghi, S.,Thompson, J.R.,Isaya, G.
Architecture of the Yeast Mitochondrial Iron-Sulfur Cluster Assembly Machinery: the Sub-Complex Formed by the Iron Donor, Yfh1, and the Scaffold, Isu1
J. Biol. Chem., 291:10378-10398, 2016

PubMed Abstract: The biosynthesis of Fe-S clusters is a vital process involving the delivery of elemental iron and sulfur to scaffold proteins via molecular interactions that are still poorly defined. We reconstituted a stable, functional complex consisting of the iron donor, Yfh1 (yeast frataxin homologue 1), and the Fe-S cluster scaffold, Isu1, with 1:1 stoichiometry, [Yfh1]24·[Isu1]24 Using negative staining transmission EM and single particle analysis, we obtained a three-dimensional reconstruction of this complex at a resolution of ∼17 Å. In addition, via chemical cross-linking, limited proteolysis, and mass spectrometry, we identified protein-protein interaction surfaces within the complex. The data together reveal that [Yfh1]24·[Isu1]24 is a roughly cubic macromolecule consisting of one symmetric Isu1 trimer binding on top of one symmetric Yfh1 trimer at each of its eight vertices. Furthermore, molecular modeling suggests that two subunits of the cysteine desulfurase, Nfs1, may bind symmetrically on top of two adjacent Isu1 trimers in a manner that creates two putative [2Fe-2S] cluster assembly centers. In each center, conserved amino acids known to be involved in sulfur and iron donation by Nfs1 and Yfh1, respectively, are in close proximity to the Fe-S cluster-coordinating residues of Isu1. We suggest that this architecture is suitable to ensure concerted and protected transfer of potentially toxic iron and sulfur atoms to Isu1 during Fe-S cluster assembly.

PubMed: 26941001
DOI: 10.1074/jbc.M115.712414

Experimental method

ELECTRON MICROSCOPY (17.5 Å)