title: Exploiting Bacterial Operons To Illuminate Human Iron-Sulfur Proteins.
abstract: Organisms from all kingdoms of life use iron-sulfur proteins (FeS-Ps) in a multitude of functional processes. We applied a bioinformatics approach to investigate the human portfolio of FeS-Ps. Sixty-one percent of human FeS-Ps bind Fe4S4 clusters, whereas 39% bind Fe2S2 clusters. However, this relative ratio varies significantly depending on the specific cellular compartment. We compared the portfolio of human FeS-Ps to 12 other eukaryotes and to about 700 prokaryotes. The comparative analysis of the organization of the prokaryotic homologues of human FeS-Ps within operons allowed us to reconstruct the human functional networks involving the conserved FeS-Ps common to prokaryotes and eukaryotes. These functional networks have been maintained during evolution and thus presumably represent fundamental cellular processes. The respiratory chain and the ISC machinery for FeS-P biogenesis are the two conserved processes that involve the majority of human FeS-Ps. Purine metabolism is another process including several FeS-Ps, in which BOLA proteins possibly have a regulatory role. The analysis of the co-occurrence of human FeS-Ps with other proteins highlighted numerous links between the iron-sulfur cluster machinery and the response mechanisms to cell damage, from repair to apoptosis. This relationship probably relates to the production of reactive oxygen species within the biogenesis and degradation of FeS-Ps.
authors.affiliation: Magnetic Resonance Center and ‡Department of Chemistry, University of Florence , 50019 Sesto Fiorentino, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Andreini
authors.affiliation: Magnetic Resonance Center and ‡Department of Chemistry, University of Florence , 50019 Sesto Fiorentino, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Banci
authors.affiliation: Magnetic Resonance Center and ‡Department of Chemistry, University of Florence , 50019 Sesto Fiorentino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
mesh_terms: D017209:Apoptosis / Q000235:genetics; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D001105:Archaea / Q000235:genetics / Q000378:metabolism; D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D005075:Biological Evolution; D002467:Cell Nucleus / Q000378:metabolism; D019295:Computational Biology; D003593:Cytoplasm / Q000378:metabolism; D004579:Electron Transport / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009876:Operon; D017433:Protein Structure, Secondary; D017382:Reactive Oxygen Species / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D040681:Structural Homology, Protein; D014584:User-Computer Interface
chemical_list: D001426:Bacterial Proteins; D007506:Iron-Sulfur Proteins; D017382:Reactive Oxygen Species
keywords: 2Fe−2S; 4Fe−4S; Fe2S2; Fe4S4; biogenesis; bioinorganic chemistry; iron; mitochondrion; respiration