Mechanism and Structural Dynamics of Translation

翻译的机制和结构动力学

• 批准号: RGPIN-2016-05199
• 负责人: Wieden, HansJoachim
• 金额: $ 3.93万
• 依托单位: University of Lethbridge
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629985
• 关键词: Mechanism; Structural; Dynamics; Translation

Understanding and describing the dynamic properties underlying the design of macromolecular machines is a current frontier in biophysical research and biomolecular engineering. The proposed research focuses on the cellular components that are part of the cells machinery to decode genetic information and to synthesize functional proteins during a process called translation. Translation takes part at the ribosome, a large macromolecular complex that is essential to all living cells. The ribosome is composed of proteins and RNAs, the two major classes of functional biomolecules. Structural studies have revealed that the ribosome is a highly dynamic biomolecular assembly line in which the two key functions (peptide-bond formation and decoding) seem to be carried out solely by RNA. However, for the rapid and accurate translation observed in living cells, additional protein factors are required. Initiation (IF) and release factors (RF) are involved in initiation and termination of protein synthesis, whereas elongation factors (EF) are required for the cyclic process of peptide chain elongation. Many of these translation factors are nucleotide hydrolases that function as molecular switches, responding to a particular input signal with a specific output. The dynamics of these information processing and decision-making events is of great interest for our understanding of translation and the design principles underlying the performance of biomolecular machines. We are just beginning to understand how the design of highly dynamic networks relaying information at the molecular scale is involved in molecular process such as translation. The proposed research will therefore target these communication networks and provide molecular tools enabling their detailed analysis.

理解和描述大分子机器设计背后的动态特性是生物物理研究和生物分子工程的当前前沿。拟议的研究重点关注细胞成分，这些细胞成分是细胞机器的一部分，可在翻译过程中解码遗传信息并合成功能性蛋白质。翻译在核糖体中进行，核糖体是一种对所有活细胞都至关重要的大分子复合物。核糖体由蛋白质和RNA组成，这是两大类功能性生物分子。结构研究表明，核糖体是一条高度动态的生物分子装配线，其中两个关键功能（肽键形成和解码）似乎仅由 RNA 执行。然而，为了在活细胞中观察到快速准确的翻译，需要额外的蛋白质因子。起始因子（IF）和释放因子（RF）参与蛋白质合成的起始和终止，而延伸因子（EF）是肽链延伸循环过程所必需的。这些翻译因子中有许多是核苷酸水解酶，它们充当分子开关，以特定的输出响应特定的输入信号。这些信息处理和决策事件的动态对于我们理解翻译和生物分子机器性能的设计原理非常重要。我们才刚刚开始了解在分子尺度上传递信息的高度动态网络的设计如何参与翻译等分子过程。因此，拟议的研究将针对这些通信网络，并提供能够对其进行详细分析的分子工具。