title: Interaction of selenoprotein W with 14-3-3 proteins: a computational approach.
abstract: SelW, a protein containing a selenocysteine (Sec) in a conserved Cys-X-X-Sec motif, has been suggested to have an antioxidant role in cell metabolism. SelW is known to specifically interact with different isoforms of 14-3-3 proteins. The latter are involved in several cellular processes such as regulation of the cell cycle, metabolism control, apoptosis, protein trafficking, and gene transcription. 14-3-3 proteins feature a conserved solvent-exposed cysteine residue, in a surface environment prone to induce chemical modifications of the thiol functionality following oxidative stress. The structures of 12 homologous complexes between SelW and 14-3-3 were calculated using sequential alignments, molecular modeling, and docking algorithms guided by known experimental NMR data. These structures reveal the viability of a protein complex in which the conserved Sec residue on SelW approaches the conserved exposed Cys on 14-3-3, making a plausible Sec-Se-S-Cys bond. On the basis of the structural information derived from these calculations, we propose a working hypothesis that entails a role for SelW as a physiological partner of 14-3-3 proteins, able to facilitate a redox-based regulation mechanism.
authors.affiliation: Laboratory of Bioinorganic Chemistry, University of Bologna, Via Fanin 40, I-40127 Bologna, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Musiani
authors.forename: Stefano
authors.initials: S
authors.lastname: Ciurli
authors.forename: Alexander
authors.initials: A
authors.lastname: Dikiy
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051151:Selenoprotein W / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D048948:14-3-3 Proteins; D020033:Protein Isoforms; D051151:Selenoprotein W