title: Identification of New Potential Interaction Partners for Human Cytoplasmic Copper Chaperone Atox1: Roles in Gene Regulation?
abstract: The human copper (Cu) chaperone Atox1 delivers Cu to P1B type ATPases in the Golgi network, for incorporation into essential Cu-dependent enzymes. Atox1 homologs are found in most organisms; it is a 68-residue ferredoxin-fold protein that binds Cu in a conserved surface-exposed Cys-X-X-Cys (CXXC) motif. In addition to its well-documented cytoplasmic chaperone function, in 2008 Atox1 was suggested to have functionality in the nucleus. To identify new interactions partners of Atox1, we performed a yeast two-hybrid screen with a large human placenta library of cDNA fragments using Atox1 as bait. Among 98 million fragments investigated, 25 proteins were found to be confident interaction partners. Nine of these were uncharacterized proteins, and the remaining 16 proteins were analyzed by bioinformatics with respect to cell localization, tissue distribution, function, sequence motifs, three-dimensional structures and interaction networks. Several of the hits were eukaryotic-specific proteins interacting with DNA or RNA implying that Atox1 may act as a modulator of gene regulation. Notably, because many of the identified proteins contain CXXC motifs, similarly to the Cu transport reactions, interactions between these and Atox1 may be mediated by Cu.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala 751 23, Sweden. helena.ohrvik@imbim.uu.se.
authors.forename: Helena
authors.initials: H
authors.lastname: Öhrvik
authors.affiliation: Department of Chemistry, Umeå University, Umeå 901 87, Sweden. pernilla.wittung@umu.se.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wittung-Stafshede
mesh_terms: D019295:Computational Biology; D003300:Copper / Q000378:metabolism*; D000079922:Copper Transport Proteins; D003593:Cytoplasm / Q000378:metabolism*; D030562:Databases, Protein; D005786:Gene Expression Regulation; D006801:Humans; D056511:Metallochaperones / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques
chemical_list: C474500:ATOX1 protein, human; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D018832:Molecular Chaperones; D003300:Copper
keywords: Atox1; bioinformatics; copper chaperone; transcription factor; two-hybrid screen