Regulation of protein synthesis during quiescence in bacteria

细菌静止期间蛋白质合成的调节

• 批准号: 10553221
• 负责人: JONATHAN DWORKIN
• 金额: $ 40.26万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-17 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10553221
• 关键词: Accounting; Anabolism; Bacillus subtilis; Bacteria; Cells; Coupled; Energy consumption; Ensure; Environment; Genetic Transcription; Goals; Growth; Life; Metabolic; Metabolism; Nucleotides; Nutrient; Post-Transcriptional Regulation; Process; Protein Biosynthesis; Regulation; Research Proposals; Research Subjects; Resources; Resuscitation; Ribosomes; Role; Starvation; Translations; attenuation; cost; improved; microbial

Project Summary Protein synthesis is subject to elaborate transcriptional and post-transcriptional regulation in growing bacterial cells. Such mechanisms ensure that protein synthesis is efficiently coupled to the needs of a rapidly dividing cell when nutrients are not limiting. However, most microbial life exists in a non- proliferating state of quiescence that enables survival during nutrient limitation and in stressful environments. Thus, the needs of quiescent cells are rather different from growing cells as they must minimize energy consumption so as to maximize available resources over a potentially extended period. Protein synthesis is the most energy intensive metabolic process in a cell, accounting for as much as ~70% of total energy consumption in bacteria. Consistently, many bacteria such as Bacillus subtilis are known to substantially reduce protein synthesis when they exit exponential growth. However, quiescent cells need to effectively exploit the emergence of favorable conditions and undergo resuscitation, so this attenuation needs to be rapidly reversible. In addition, as the ribosome is itself the most energetically costly macromolecular machine to synthesize, it must be protected from any degradative processes. And, as with translational attenuation, this protection must be compatible with efficient re-initiation of protein synthesis when conditions improve. Thus, both the inhibitory and protective mechanisms need to be quickly reversible. How the cell balances these two goals is the subject of this research proposal. First, we examine how ribosomes are protected from degradation under metabolic conditions where de novo ribosome biosynthesis is limited. Second, we investigate a reversible mechanism of translation inactivation with particular focus on the role of the nucleotide (p)ppGpp.

项目摘要 蛋白质合成在生长过程中受到复杂的转录和转录后调控 细菌细胞这样的机制确保蛋白质合成有效地与生物体的需要相结合。 当营养物质不受限制时，细胞迅速分裂。然而，大多数微生物存在于非- 在营养限制和压力下能够生存的静止增殖状态 环境.因此，静止细胞的需求与生长细胞的需求是相当不同的，因为它们必须 最大限度地减少能源消耗，以最大限度地利用现有资源， 期蛋白质合成是细胞中能量最密集的代谢过程， 约占细菌总能量消耗的70%。然而，许多细菌，如芽孢杆菌， 已知枯草杆菌在退出指数生长时显著减少蛋白质合成。 然而，静止细胞需要有效地利用有利条件的出现， 因此这种衰减需要迅速逆转。此外，作为核糖体， 它本身是合成能量最昂贵的高分子机器，必须保护它免受 任何降解过程。而且，与平移衰减一样，这种保护必须兼容 当条件改善时有效地重新启动蛋白质合成。因此，抑制和 保护机制需要快速可逆。细胞如何平衡这两个目标是 本研究课题。首先，我们研究核糖体是如何被保护不被降解的 在从头核糖体生物合成受到限制的代谢条件下。第二，我们调查一个 翻译失活的可逆机制，特别关注核苷酸的作用 （p）ppGpp。