Selenium metabolism in bacteria

Abstract

The biosynthesis and specific incorporation of selenocysteine into protein in bacteria requires the function of two cis and four trans elements. The cis elements are a UGA codon determining the position of selenocysteine insertion into the nascent polypeptide and a secondary/tertiary structure within the mRNA, designated the SECIS element, following the UGA at its 3′side. The trans elements consist of a tRNA species, tRNASec, which is charged by the cellular seryl-tRNA synthetase and serves as an adaptor for the conversion of the seryl moiety into the selenocysteyl product, catalysed by the biosynthetic enzyme selenocysteine synthase. Monoselenophosphate, provided by selenophosphate synthetase, is the selenium donor species. Selenocysteyl-tRNASec is bound by the special translation factor SelB which in its N-terminal part displays sequence similarity to elongation factor Tu. With its C-terminal 17 kDa domain, SelB binds to the apical part of the SECIS stem-loop structure thus forming a quaternay complex with the two nucleic acids and the guanosine nucleotide. Besides tethering the charged tRNA to the ribosomal A-site, binding to the SECIS confers to SelB a conformation competent for interaction with the ribosome. SECIS binding also stabilizes the interaction of SelB with charged tRNA. Selenocysteine insertion is competing with termination at the UGA codon whereby competition is influenced by codon context, the two amino acids preceding selenocysteine in the polypeptide and the balance of the components of the insertion machinery. Selenocysteine insertion in archaea resembles the eucaryal situation in that the SECIS element is localized in the 3′untranslated region of the mRNA. The archaeal homolog of SelB is unable to recognize the SECIS motif and may require the function of a second protein, as has been shown to be the case for the mammalian counterpart.