The Head of the tRNase Z Recognition and Binding Domain

描述（由申请人提供）：转移RNA被转录为具有5'和3'末端延伸的前体，其必须通过加工去除。在pre-tRNA成熟途径中，tRNase Z切割受体茎3'端以外的一个核苷酸，内切核酸去除3'端尾部。识别和结合结构域（RBD）从远离活性位点的tRNase Z的体中挤出。共晶结构表明，RBD的球状头部主要与tRNA手肘（D/T环）结合，远离易断裂的键。我们提出了三个问题来研究tRNase Z的RBD：（1）RBD头部的每个残基如何有助于底物结合和催化？(2)RBD是一个独立的折叠单元吗？(3)RBD和pre-tRNA之间的联系是什么？这项研究将揭示一种新的机制，底物识别。 转运RNA（tRNA）是蛋白质合成过程的核心。tRNA的突变与母系传播的线粒体疾病和综合征有关。此外，编码tRNase Z（tRNA成熟途径中的一种酶）的基因与前列腺癌风险升高有关，使拟议的研究具有生物医学相关性。

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.