Crystal Structure Analyses of Selenoprotein Biosynthesis

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Crystal structures of protein and RNA components involved in the biosynthesis of selenocysteine and its cotranslational incorporation into selenoproteins in the Archaeon Methanococcus jannaschii and the Bacterium Eubacterium acidaminophilum shall be determined. The pertaining factors are selenocysteine synthase (SelA), elongation factor SelB, tRNASec (SelC), seryltRNA synthetase (SerRS), and selenophosphate synthetase (SelD). Aims of the projects are to explore the mechanistics of selenocysteine synthesis by SelA, to elucidate the structural peculiarities of the selenocysteine specific tRNASec, to understand its discrimination by seryl-tRNA synthetase, by selenocysteine synthase, and by elongation factor SelB, to structurally clarify the interactions of SelB with mRNA SECIS-elements, and to explain the mechanism of synthesis of the activated selenium donor, selenophosphate, by selenophosphate synthetase. The structures shall aid in understanding the mechanisms of this unique expansion of the genetic code and in characterizing the corresponding systems in higher organisms.