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

• 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
• 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

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.

摘要 核糖体由核糖核蛋白组成，对蛋白质的生物合成是必不可少的，这是 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70年代核糖体。70年代的核糖体是由 由两个亚基组成，分别称为30s(小)和50s核糖体(大)亚单位。最小亚基为 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多个核心r-蛋白。核糖体不是一个固定的实体，相反，它是 适应引起核糖体异质性的不断变化的环境。此外，还有几个小的 辅助蛋白调节核糖体的生物发生、循环和功能；其中许多蛋白质 它们的分子功能还有待发现。 在蛋白质合成过程中，翻译保真度保持了很高的准确性。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到10-3 费率。保持适当的翻译保真度需要氨基酸和tRNA的同源配对 氨基酰-tRNA合成酶和相应的氨基酸-tRNA合成酶对mRNA密码子的准确解码 核糖体上的tRNA。几种核心和辅助r-蛋白驱动密码子的正确解码 保持翻译的保真度。各种应激状态，如营养和氧化应激，通常 导致细菌的误译和生长缺陷。我们最近确定了几个因素，包括 变形链球菌(口腔病原体)所需的保守新蛋白SprV(90个氨基酸) 用于翻译保真度、压力容忍度和适应能力。这项研究的主要目标是了解 在分子水平上，SprV和其他辅助蛋白如L9(R蛋白)和EF-P是如何调节的 翻译保真度改变口腔链球菌的生理和生物适合性。