title: The role of the hybrid cluster protein in oxidative stress defense.
abstract: Hybrid cluster proteins (HCP) contain two types of Fe/S clusters, namely a [4Fe-4S](2+/1+) or [2Fe-2S](2+/1+) cluster and a novel type of hybrid cluster, [4Fe-2S-2O], in the as-isolated state. Although first isolated from anaerobic sulfate-reducing bacteria, the analysis of the genomic sequences reveals that genes encoding putative hybrid cluster proteins are present in a wide range of organisms, aerobic, anaerobic, or facultative, from the Bacteria, Archaea, and Eukarya domains. Despite a detailed spectroscopic and structural characterization, the precise physiological function of these proteins remained unknown. The present work shows that the transcription of the Escherichia coli hcp gene is induced by hydrogen peroxide, and this induction is regulated by the redox-sensitive transcriptional activator, OxyR. The E. coli hcp mutant strain exhibits higher sensitivity to hydrogen peroxide, a behavior that reverts to the wild type phenotype once a plasmid carrying the hcp gene is reintroduced. Furthermore, the purified HCPs from E. coli and Desulfovibrio desulfuricans ATCC 27774 show an alternative enzymatic activity, which under physiological conditions exhibited K(m) values for hydrogen peroxide (approximately 0.3 mM) within the range of other peroxidases. Altogether, the results reveal that HCP is involved in oxidative stress protection.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: Cláudia C
authors.initials: CC
authors.lastname: Almeida
authors.forename: Célia V
authors.initials: CV
authors.lastname: Romão
authors.forename: Peter F
authors.initials: PF
authors.lastname: Lindley
authors.forename: Miguel
authors.initials: M
authors.lastname: Teixeira
authors.forename: Lígia M
authors.initials: LM
authors.lastname: Saraiva
mesh_terms: D045285:Desulfovibrio desulfuricans; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008956:Models, Chemical; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010957:Plasmids; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018085:Regulon / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029968:Escherichia coli Proteins; D007506:Iron-Sulfur Proteins; D016877:Oxidants; D011994:Recombinant Proteins; D015534:Trans-Activators; D006861:Hydrogen Peroxide