ATOMIC RESOLUTION STRUCTURES OF THE ESCHERICHIA COLI 70S RIBOSOME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项工作主要集中在核糖体循环的结构基础和抗生素对核糖体循环的抑制。氨基糖苷类抗生素是一类广泛使用的抗生素，可导致信使RNA解码错误，阻断mRNA和转移RNA易位，抑制核糖体循环。核糖体回收是在蛋白质合成终止后进行的，并由细菌中的核糖体回收因子(RRF)辅助。氨基糖苷类药物抑制核糖体循环的分子机制尚不清楚。在NE-CAT APS光束线上测量的数据使我们在大肠杆菌70S核糖体的X射线晶体结构中显示，RRF结合导致对亚基结合至关重要的大核糖体亚基的RNA螺旋H69从亚基界面摆动。氨基糖苷类与H69结合，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抑制核糖体循环提供了结构上的解释。

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.