New targets for antibiotics: self assembling ribonucleoprotein complexes

描述（由申请人提供）：核糖体是执行基本生物学任务的分子机器：它们合成蛋白质。因此，细菌核糖体是抗生素的合理靶点。然而，耐药细菌的出现（和生长）对人类健康构成了重大威胁。必须开发新的策略来攻击耐药菌株。最近，突破性的核糖体结构研究使一个全新的方法来干扰核糖体：阻止其自我组装。在这里，我们建议开发和应用一种新的实验方法来测量伴随着核糖体或其亚基的真实的时间自组装的结构变化。如果成功，这种方法将能够识别可能受到攻击的折叠途径或部分折叠状态。公共卫生相关性：大型分子机器，如核糖体，由RNA和蛋白质前体构成。我们提出的方法将提供独特的见解大型核糖核蛋白复合物的自组装，如核糖体。这项工作的长期目标是指导新一代干扰自组装的抗生素的开发。如果这种方法成功，这一知识将为对抗抗生素耐药性细菌带来额外的武器，这对人类健康的威胁不断升级。

DESCRIPTION (provided by applicant): Ribosomes are molecular machines that carry out an essential biological task: they synthesize proteins. Thus, bacterial ribosomes are logical targets for antibiotics. However, the emergence (and growth of) drug resistant bacteria poses a major threat to human health. New strategies for attacking resistant strains must be developed. Recent, breakthrough structural studies of the ribosome enable an entirely new approach to interfering with the ribosome: preventing its self assembly. Here, we propose to develop and apply a new experimental method for measuring structural changes accompanying the real time self-assembly of the ribosome or its subunits. If successful, this approach will enable identification of folding pathways or partially folded states that may be amenable to attack. PUBLIC HEALTH RELEVANCE: Large molecular machines, like the ribosome, are constructed from both RNA and protein precursors. The methods we propose will provide unique insight into self-assembly of large ribonucleoprotein complexes, like the ribosome. A long term goal of this work is to guide development of a new generation of antibiotics that interfere with self-assembly. If the approach is successful, this knowledge brings an additional weapon to the fight against antibiotic resistant bacteria, an escalating threat to human health.