Analytical Ultracentrifugation of Biomolecules and Macromolecular Complexes

蛋白质的构象状态是调控生物过程的重要机制。大多数蛋白质在其功能循环过程中会经历一系列结构变化，以适应与其他分子（如脂质、蛋白质和核酸）的结合和修饰，从而产生特定的结果。因此，蛋白质不能采用特定的构象具有重要的意义，特别是在疾病的发生和进展方面。分析性超离心（AUC）是一种相对简单、功能强大的方法，能够在不影响样品完整性的情况下评估和区分蛋白质的不同构象状态。此外，AUC高度适用于确定其他参数，包括蛋白质的大小和形状，并能够确定其他分子如何影响这些属性。这里所要求的AUC设备将为我们的研究项目增加巨大的价值，这些研究项目在很大程度上根植于理解蛋白质是如何通过改变它们的构象和寡聚态来调节的，以及这些特征如何与生物功能相关。本提案的资助将为我们实验室的研究人员（学生，技术人员和博士后研究员）提供一个持续的机会，以获得现代蛋白质结构和功能研究中最广泛使用的方法之一的宝贵培训。随时可以使用AUC机器将有助于为他们作为科学研究人员的职业生涯增加价值。

The conformational status of proteins is an important mechanism by which biological processes are regulated. Most proteins go through a series of structural changes in the course of their functional cycle to accommodate binding to, and modification by, other molecules such as lipids, proteins, and nucleic acids to produce specific outcomes. Therefore, the inability for proteins to adopt particular conformations has important implications, particularly with respect to disease development and progression. Analytical ultracentrifugation (AUC) is a relatively simple, powerful method that is capable of assessing and distinguishing between different conformational states of proteins without compromising sample integrity. Moreover, AUC is highly amenable for the determination of other parameters, including size and shape of the protein, and in being able to establish how other molecules affect these attributes. The AUC equipment requested here will add tremendous value to our research programs, which are heavily rooted in understanding how proteins are regulated via changes to their conformational and oligomeric states as well as how such features correlate to biological function. Funding of this proposal will provide a continuing opportunity for the research personnel in our laboratories (students, technicians and post-doctoral fellows) to gain valuable training with one of the most widely used approaches in modern protein structure and function studies. Ready access to an AUC machine will serve to add value to their careers as scientific researchers.