Mechanisms of translational control

延伸因子P（EF-P）是一种普遍保守的蛋白质，它可以缓解人的免疫缺陷。 核糖体通过与核糖体结合和熵刺激肽键在聚脯氨酸基序处暂停 阵在迄今为止表征的所有实施例中，EF-P及其同系物需要翻译后修饰 才能正常工作EF-P修饰的功能和修饰改善的机制 翻译效率不明确。编码EF-P（efp）或相应的 修饰途径是高度多效性的，导致多种有害表型，包括减缓 生长、丧失运动性、减弱的毒力和对抗生素的超敏反应。的初步鉴定 枯草芽孢杆菌EF-P的翻译后修饰，其需要添加5-氨基戊醇以获得活性， 挑战了EF-P仅用于维持基本细胞功能的概念。在B。枯草杆菌的比率 修饰为未修饰的EF-P随生长阶段而变化，并且EF-P的缺失或EF-P的去除都不影响生长。 修饰损害营养生长，而是特别损害运动发育。我们假设， 基于允许的翻译后修饰基团的化学多样性，EF-P修饰是 监管。B。枯草芽孢杆菌是一个理想的模式生物，以探讨这一假设的缺陷，无论是在EF-P或EF-P 修饰损害群集运动，一个强大的表型无偏见的遗传选择。的目标 本研究的目的是通过研究EF-P的不同结构和功能， 这种保守的、普遍存在的翻译因子在蛋白质合成过程中发挥作用的机制。 具体来说，我们将确定EF-P如何作为细胞分化特异性翻译因子， 探讨EF-P的翻译调控机制。

Elongation Factor P (EF-P) is a universally conserved post-translationally modified protein that relieves ribosomal pausing at polyproline motifs by binding to the ribosome and entropically stimulating peptide bond formation. In all examples characterized to date EF-P and its homologs require post-translational modification to be functional. The function of EF-P modifications and the mechanism by which modifications would improve translation efficiency is unclear. Mutations in bacterial genes encoding EF-P (efp) or the corresponding modification pathways are highly pleiotropic, leading to a variety of detrimental phenotypes including slowed growth, loss of motility, attenuated virulence and hypersensitivity to antibiotics. Preliminary characterization of post-translational modification of Bacillus subtilis EF-P, which requires 5-aminopentanol addition for activity, challenges the notion that EF-P functions solely to maintain basic cellular function. In B. subtilis the ratio of modified to unmodified EF-P varies with growth phase, and neither deletion of EF-P nor removal of the modification impair vegetative growth, but instead specifically impair motility development. We hypothesize, based on the chemical diversity of permissive post-translational modification groups, that EF-P modification is regulatory. B. subtilis is an ideal model organism to explore this hypothesis as defects in either EF-P or EF-P modification impair swarming motility, a powerful phenotype for unbiased genetic selection. The objectives of this proposal are to uncover the structural and functional diversity of EF-P by investigating the different mechanisms by which this conserved, ubiquitous, translation factor functions during protein synthesis. Specifically, we will determine how EF-P acts as a cellular differentiation-specific translation factor and investigate the mechanism of translational control by EF-P.