CRYSTAL STRUCTURE OF METHIONYL-TRNA SYNTHETASE COMPLEXED WITH TRNA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。作为蛋白质生物合成的第一步，氨基酰-tRNA合成酶催化氨基酸与同源tRNA的结合。氨基酰化必须是特异和有效的，才能使蛋白质的合成既快速又准确。根据已知的蛋白质-RNA复合体特别是氨基酰基-tRNA复合体的构象变化，我们假设甲硫酰-tRNA合成酶(MetRS)的有效催化需要tRNA和MetRs的构象重排，这是由同源反密码子结合引起的。这种相互诱导的tRNA和MetRS的匹配可能推动了MetRS C-末端结构域的反密码子结合部位和酶的催化活性部位之间的远程通讯，位于约75？离开。为了可视化tRNA与MetRS结合时的构象变化和结构域间的通讯，我们正在研究E.ColiMetRS：tRNA复合体的晶体结构。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aminoacyl-tRNA synthetases catalyze the attachment of amino acid to cognate tRNA as the first step in protein biosynthesis. Aminoacylation must be specific and efficient for protein synthesis to be both fast and accurate. Based on the known conformational changes that occur in protein-RNA complexes in general and aminoacyl-tRNA complexes in particular, we hypothesize that efficient catalysis by methionyl-tRNA synthetase (MetRS) requires conformational rearrangements of both tRNA and MetRS, induced by cognate anticodon binding. This proposed mutually induced fit of the tRNA and MetRS probably drives long-range communication between the anticodon-binding site in the C-terminal domain of MetRS and the catalytic active site of the enzyme, located approximately 75 ? away. To visualize the conformational change and the inter-domain communication upon tRNA binding to MetRS, we are pursuing to determine the crystal structure of the E. coli MetRS:tRNA complex.