ATOMIC RESOLUTION STRUCTURES OF THE ESCHERICHIA COLI 70S RIBOSOME

大肠杆菌 70S 核糖体的原子分辨率结构

• 批准号: 8169238
• 负责人: JAMIE HD CATE
• 金额: $ 1.4万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169238
• 关键词: Aminoglycosides; Antibiotics; Bacteria; Binding; Computer Retrieval of Information on Scientific Projects Database; Data; Escherichia coli; Funding; Grant; Institution; Measures; Messenger RNA; Molecular; Protein Biosynthesis; RNA; Recycling; Research; Research Personnel; Resolution; Resources; Ribosomes; Roentgen Rays; Source; Structure; Transfer RNA; United States National Institutes of Health; Work; base; beamline; ribosome releasing factor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This work focused on primarily on the structural basis for ribosome recycling and antibiotic inhibition of ribosome recycling. Aminoglycosides are widely used antibiotics that cause messenger RNA decoding errors, block mRNA and transfer RNA translocation, and inhibit ribosome recycling. Ribosome recycling follows the termination of protein synthesis and is aided by ribosome recycling factor (RRF) in bacteria. The molecular mechanism by which aminoglycosides inhibit ribosome recycling had remained unknown. Data measured at the NE-CAT APS beamlines allowed us to show in X-ray crystal structures of the Escherichia coli 70S ribosome that RRF binding causes RNA helix H69 of the large ribosomal subunit, which is crucial for subunit association, to swing away from the subunit interface. Aminoglycosides bind to H69 and completely restore the contacts between ribosomal subunits that are disrupted by RRF. These results provide a structural explanation for aminoglycoside inhibition of ribosome recycling.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项工作主要集中在核糖体再循环的结构基础和核糖体再循环的抗生素抑制。 氨基糖苷类抗生素是一种广泛使用的抗生素，可导致信使RNA解码错误，阻断mRNA和转运RNA易位，并抑制核糖体再循环。 核糖体再循环在蛋白质合成终止后进行，并由细菌中的核糖体再循环因子（RRF）辅助。 氨基糖苷类药物抑制核糖体再循环的分子机制仍不清楚。 在NE-CAT APS光束线测量的数据使我们能够在大肠杆菌70 S核糖体的X射线晶体结构中显示，RRF结合导致核糖体大亚基的RNA螺旋H69，这对亚基缔合至关重要，从亚基界面摆动。 氨基糖苷类与H69结合并完全恢复被RRF破坏的核糖体亚基之间的接触。 这些结果为氨基糖苷类抑制核糖体再循环提供了结构上的解释。