Crystal Structure Analyses of Selenoprotein Biosynthesis

应确定参与硒代半胱氨酸生物合成及其共翻译掺入詹氏甲烷球菌和嗜酸氨基真杆菌中硒蛋白的蛋白质和RNA组分的晶体结构。相关因子为硒代半胱氨酸合成酶（SelA）、延伸因子SelB、tRNASec（SelC）、丝氨酸tRNA合成酶（SerRS）和硒磷酸合成酶（SelD）。本项目的目的是探索SelA合成硒代半胱氨酸的机制，阐明硒代半胱氨酸特异性tRNASec的结构特点，了解其被丝氨酸-tRNA合成酶、硒代半胱氨酸合成酶和延伸因子SelB的区分，从结构上阐明SelB与mRNA SECIS元件的相互作用，并解释活化硒供体硒磷酸的合成机制，硒磷酸合成酶。这些结构将有助于理解遗传密码这种独特扩展的机制，并有助于描述高等生物体中相应系统的特征。

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.