Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly. 2010

Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, Detroit, Michigan 48201, USA.

Frataxin, a conserved nuclear-encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich's ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone in the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural module to improve our understanding of the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry. Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into an Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D002151 Calorimetry The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D000096923 Frataxin A protein involved in the transfer of iron and sulfur to iron-sulfur cluster (ISC) assembly complex for de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. Deficiency leads to the neurodegenerative disease FRIEDREICH ATAXIA. FXN Frataxin,Frataxin Protein,Friedreich Ataxia Protein,Ataxia Protein, Friedreich,Frataxin, FXN,Protein, Frataxin,Protein, Friedreich Ataxia
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D013050 Spectrometry, Fluorescence Measurement of the intensity and quality of fluorescence. Fluorescence Spectrophotometry,Fluorescence Spectroscopy,Spectrofluorometry,Fluorescence Spectrometry,Spectrophotometry, Fluorescence,Spectroscopy, Fluorescence
D046912 Multiprotein Complexes Macromolecular complexes formed from the association of defined protein subunits. Macromolecular Protein Complexes,Complexes, Macromolecular Protein,Complexes, Multiprotein,Protein Complexes, Macromolecular
D056928 X-Ray Absorption Spectroscopy Analysis of the energy absorbed across a spectrum of x-ray energies/wavelengths to determine the chemical structure and electronic states of the absorbing medium. Near Edge X-Ray Absorption Fine Structure Spectroscopy,NEXAFS Spectroscopy,Near-Edge X-Ray Absorption Fine Structure Spectroscopy,X-Ray Absorption Near Edge Structure Spectroscopy,X-Ray Absorption Near-Edge Structure Spectroscopy,XANES Spectroscopy,Absorption Spectroscopy, X-Ray,Near Edge X Ray Absorption Fine Structure Spectroscopy,Spectroscopy, NEXAFS,Spectroscopy, X-Ray Absorption,Spectroscopy, XANES,X Ray Absorption Near Edge Structure Spectroscopy,X Ray Absorption Spectroscopy
D019906 Nuclear Magnetic Resonance, Biomolecular NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope. Biomolecular Nuclear Magnetic Resonance,Heteronuclear Nuclear Magnetic Resonance,NMR Spectroscopy, Protein,NMR, Biomolecular,NMR, Heteronuclear,NMR, Multinuclear,Nuclear Magnetic Resonance, Heteronuclear,Protein NMR Spectroscopy,Biomolecular NMR,Heteronuclear NMR,Multinuclear NMR,NMR Spectroscopies, Protein,Protein NMR Spectroscopies,Spectroscopies, Protein NMR,Spectroscopy, Protein NMR
D024101 Mitochondrial Proteins Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA. Proteins, Mitochondrial,Mitochondrial Protein,Protein, Mitochondrial
D029701 Saccharomyces cerevisiae Proteins Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes. Baker's Yeast Proteins,S cerevisiae Proteins

Related Publications

Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
June 2021, International journal of molecular sciences,
Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
September 2003, EMBO reports,
Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
November 2019, Metallomics : integrated biometal science,
Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
February 2007, EMBO reports,
Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
October 2014, Nature communications,
Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
February 2022, Micron (Oxford, England : 1993),
Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
May 2008, The Journal of biological chemistry,
Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
June 2015, Biochemistry,
Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
July 2008, Biochemistry,
Jeremy D Cook, and Kalyan C Kondapalli, and Swati Rawat, and William C Childs, and Yogapriya Murugesan, and Andrew Dancis, and Timothy L Stemmler
June 2013, Molecular biology of the cell,
Copied contents to your clipboard!