BIOMAT Database Logo BIOMAT Database Logo

Molecular Details of the Frataxin-Scaffold Interaction during Mitochondrial Fe-S Cluster Assembly. 2021

Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA.

Iron-sulfur clusters are essential to almost every life form and utilized for their unique structural and redox-targeted activities within cells during many cellular pathways. Although there are three different Fe-S cluster assembly pathways in prokaryotes (the NIF, SUF and ISC pathways) and two in eukaryotes (CIA and ISC pathways), the iron-sulfur cluster (ISC) pathway serves as the central mechanism for providing 2Fe-2S clusters, directly and indirectly, throughout the entire cell in eukaryotes. Proteins central to the eukaryotic ISC cluster assembly complex include the cysteine desulfurase, a cysteine desulfurase accessory protein, the acyl carrier protein, the scaffold protein and frataxin (in humans, NFS1, ISD11, ACP, ISCU and FXN, respectively). Recent molecular details of this complex (labeled NIAUF from the first letter from each ISC protein outlined earlier), which exists as a dimeric pentamer, have provided real structural insight into how these partner proteins arrange themselves around the cysteine desulfurase, the core dimer of the (NIAUF)2 complex. In this review, we focus on both frataxin and the scaffold within the human, fly and yeast model systems to provide a better understanding of the biophysical characteristics of each protein alone and within the FXN/ISCU complex as it exists within the larger NIAUF construct. These details support a complex dynamic interaction between the FXN and ISCU proteins when both are part of the NIAUF complex and this provides additional insight into the coordinated mechanism of Fe-S cluster assembly.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D007506 Iron-Sulfur Proteins A group of proteins possessing only the iron-sulfur complex as the prosthetic group. These proteins participate in all major pathways of electron transport: photosynthesis, respiration, hydroxylation and bacterial hydrogen and nitrogen fixation. Iron-Sulfur Protein,Iron Sulfur Proteins,Iron Sulfur Protein,Protein, Iron-Sulfur,Proteins, Iron Sulfur,Proteins, Iron-Sulfur,Sulfur Proteins, Iron
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D013437 Carbon-Sulfur Lyases Enzymes that catalyze the cleavage of a carbon-sulfur bond by means other than hydrolysis or oxidation. EC 4.4. Sulfhydrases,Carbon Sulfur Lyases,Lyases, Carbon-Sulfur
D013455 Sulfur An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight [32.059; 32.076]. It is found in the amino acids cysteine and methionine. Sulfur-16,Sulfur 16
D046912 Multiprotein Complexes Macromolecular complexes formed from the association of defined protein subunits. Macromolecular Protein Complexes,Complexes, Macromolecular Protein,Complexes, Multiprotein,Protein Complexes, Macromolecular
D033862 Iron-Binding Proteins Proteins that specifically bind to IRON. Iron-Binding Protein,Iron Binding Protein,Iron Binding Proteins,Protein, Iron-Binding

Related Publications

Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly.
October 2010, Biochemistry,
Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Mapping iron binding sites on human frataxin: implications for cluster assembly on the ISU Fe-S cluster scaffold protein.
June 2008, Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry,
Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Binding of yeast frataxin to the scaffold for Fe-S cluster biogenesis, Isu.
May 2008, The Journal of biological chemistry,
Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Trading Places-Switching Frataxin Function by a Single Amino Acid Substitution within the [Fe-S] Cluster Assembly Scaffold.
May 2015, PLoS genetics,
Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Molecular characteristics of proteins within the mitochondrial Fe-S cluster assembly complex.
February 2022, Micron (Oxford, England : 1993),
Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Zinc and the iron donor frataxin regulate oligomerization of the scaffold protein to form new Fe-S cluster assembly centers.
June 2017, Metallomics : integrated biometal science,
Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Frataxin Accelerates [2Fe-2S] Cluster Formation on the Human Fe-S Assembly Complex.
June 2015, Biochemistry,
Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Drosophila frataxin: an iron chaperone during cellular Fe-S cluster bioassembly.
July 2008, Biochemistry,
Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Acidic residues of yeast frataxin have an essential role in Fe-S cluster assembly.
February 2007, EMBO reports,
Courtney J Campbell, and Ashley E Pall, and Akshata R Naik, and Lindsey N Thompson, and Timothy L Stemmler
Frataxin directly stimulates mitochondrial cysteine desulfurase by exposing substrate-binding sites, and a mutant Fe-S cluster scaffold protein with frataxin-bypassing ability acts similarly.
December 2013, The Journal of biological chemistry,
Copied contents to your clipboard!