The Head of the tRNase Z Recognition and Binding Domain

描述(申请人提供)：转移RNA被转录为带有5‘和3’末端延伸的前体，必须通过加工去除。在前tRNA成熟途径中，tRNase Z切割受体茎3‘端以外的一个核苷酸，内切去除3’端拖尾。识别结合结构域(RBD)从远离活性部位的tRNase Z体内挤出。共晶结构表明，RBD的球形头部主要与tRNA的肘部(D/T环)结合，远离剪切键。我们建议通过提出三个问题来研究tRNase Z的RBD：(1)RBD头部的每个残基是如何促进底物结合和催化的？(2)RBD是一个独立的折叠单位吗？(3)RBD与前tRNA之间有什么联系？这项研究将为底物识别提供一种新的机制。 转移RNA(TRNA)是蛋白质合成过程中的核心。TRNAs的突变与母体传播的线粒体疾病和综合征有关。此外，编码tRNase Z的基因，tRNA成熟途径中的一种酶，与前列腺癌风险增加有关，使拟议的研究具有生物医学意义。

DESCRIPTION (provided by applicant): Transfer RNAs are transcribed as precursors with 5' and 3' end extensions which must be removed by processing. In the pre-tRNA maturation pathway, tRNase Z cleaves one nucleotide beyond the 3' end of the acceptor stem, endonucleolytically removing the 3' end trailer. A recognition and binding domain (RBD) is extruded from the body of tRNase Z remote from the active site. A co-crystal structure suggests that the globular head of the RBD principally binds to the elbow (D/T loops) of tRNA, far from the scissile bond. We propose to investigate the RBD of tRNase Z by posing three questions: (1) How does each residue in the head of the RBD contribute to substrate binding and catalysis? (2) Is the RBD an independently folding unit? (3) What are the contacts between the RBD and pre-tRNA? This investigation will shed light on a novel mechanism for substrate recognition. Transfer RNA (tRNA) is central to the process of protein synthesis. Mutations in tRNAs are associated with maternally transmitted mitochondrial diseases and syndromes. Additionally, the gene that encodes tRNase Z, an enzyme in the tRNA maturation pathway, has been associated with an elevated risk of prostate cancer, making the proposed research biomedically relevant.