Role of translational fidelity in cellular physiology of oral streptococci

翻译保真度在口腔链球菌细胞生理学中的作用

基本信息

批准号：
10573223
负责人：
Indranil Biswas
金额：
$ 42.47万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10573223
关键词：
Affect Amino Acids Amino Acyl Transfer RNA Amino Acyl-tRNA Synthetases Antibiotics Anticodon Bacteria Biochemical Biogenesis Biological Biological Assay Biological Process Cell physiology Cells Codon Nucleotides Complex Data Defect Ensure Environment Escherichia coli Exposure to Firmicutes Genes Genetic Transcription Genetic study Genus Mycobacterium Goals Gram-Positive Bacteria Growth Heterogeneity Hibernation Homeostasis Hypothetical Protein In Vitro Life Style Link Messenger RNA Microbial Biofilms Molecular Nutrient Nutritional Oral cavity Organism Oxidative Stress Pathogenesis Pathogenicity Physiology Play Process Production Prokaryotic Cells Protein Biosynthesis Proteins Proteome RNA RNA, Ribosomal, 16S Recycling Replication Error Resistance Ribonucleoproteins Ribosomal Proteins Ribosomes Role Series Streptococcus Streptococcus mutans Streptococcus pneumoniae Streptococcus pyogenes Stress Tertiary Protein Structure Translation Process Protein Translations Virulence Virulence Factors Work antibiotic tolerance biological adaptation to stress environmental adaptation factor EF-P fitness genome wide screen in vivo macromolecule microbial novel oral pathogen oral streptococci pathogen protein function stoichiometry stress tolerance trait translation assay

项目摘要

ABSTRACT Ribosomes are composed of ribonucleoproteins and are essential for protein biosynthesis, which is one of the most complex biological processes in the cell. In prokaryotes, mature ribosomes contain proteins (r- proteins) and RNA (rRNA) that are assembled into the mature 70S ribosome. The 70S ribosomes are made by two subunits, designated as the 30S (small) and the 50S ribosome (large) subunits. The small subunit is composed of the 16S ribosomal RNA (rRNA) and over 20 core r-proteins while the large subunit is composed of 23S and 5S rRNAs, and more than 30 core r-proteins. Ribosome is not a stationary entity, rather it is adapted to changing environments giving rise to ribosome heterogeneity. Additionally, several small accessory proteins modulate the biogenesis, recycling, and function of the ribosome; many of these proteins and their molecular functions remain to be discovered. During protein synthesis, translational fidelity is maintained with high accuracy. However, the average translation error rate is relatively higher (10-4 to 10-3 per codon) compared to transcription or replication error rates. Maintaining proper translational fidelity requires cognate pairing of amino acids and tRNAs by aminoacyl-tRNA (aa-tRNA) synthetase and accurate decoding of mRNA codons by the corresponding aa- tRNAs on the ribosome. Several core and accessory r-proteins drive the correct decoding of the codons to maintain the translational fidelity. Various stress conditions such as nutritional and oxidative stresses often lead to mistranslation and growth defects in bacteria. We have recently identified several factors including a conserved novel protein, SprV (90 amino acids), in Streptococcus mutans (an oral pathogen) that is required for translational fidelity, stress tolerance and adaptation. The major goal of this study is to understand at the molecular level how SprV and other accessory proteins such as L9 (r-protein) and EF-P modulate translational fidelity to alter physiology and biological fitness of oral streptococci.

抽象的核糖体由核糖核蛋白组成，对于蛋白质生物合成至关重要，蛋白质是生物合成的重要组成部分之一细胞中最复杂的生物过程。在原核生物中，成熟的核糖体含有蛋白质（r- 蛋白质）和 RNA (rRNA)，组装成成熟的 70S 核糖体。 70S核糖体的制作由两个亚基组成，分别称为 30S（小）和 50S 核糖体（大）亚基。小亚基是由 16S 核糖体 RNA (rRNA) 和 20 多种核心 r 蛋白组成，而大亚基则由 23S 和 5S rRNA，以及 30 多种核心 r 蛋白。核糖体不是静止的实体，而是适应不断变化的环境，从而产生核糖体异质性。此外，还有几个小辅助蛋白调节核糖体的生物发生、回收和功能；许多这些蛋白质它们的分子功能仍有待发现。在蛋白质合成过程中，翻译保真度保持高精度。然而，平均与转录或复制错误相比，翻译错误率相对较高（每个密码子 10-4 至 10-3）费率。维持适当的翻译保真度需要氨基酸和 tRNA 的同源配对氨酰基-tRNA (aa-tRNA) 合成酶和相应 aa- 准确解码 mRNA 密码子核糖体上的 tRNA。一些核心和辅助 r 蛋白驱动密码子的正确解码保持翻译保真度。各种应激条件，例如营养应激和氧化应激经常导致细菌的错误翻译和生长缺陷。我们最近确定了几个因素，包括变异链球菌（口腔病原体）中所需的保守新型蛋白质 SprV（90 个氨基酸）用于翻译保真度、压力耐受性和适应。这项研究的主要目标是了解分子水平 SprV 和其他辅助蛋白（例如 L9（r 蛋白）和 EF-P）如何调节翻译保真度改变口腔链球菌的生理学和生物适应性。