Protein dynamics: from the marginally to the extremely stable

蛋白质动力学：从边缘稳定到极其稳定

• 批准号: 2205665
• 负责人: Martin Gruebele
• 金额: $ 79.51万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2205665&HistoricalAwards=false
• 关键词: Protein; dynamics; marginally; extremely; stable

We live in a world where the environment is becoming more extreme, and yet much remains to be learned about how organisms successfully adapt to extreme conditions. Dehydration, high pressure, temperature changes are all variables that resilient organisms can cope with to survive, and proteins play a particularly important role. This research project looks at how some proteins protect other proteins when the temperature goes up too high for survival, how proteins that are barely able to fold can fold in the right environment, and how microorganisms that live at high pressures and temperatures cope by harnessing the adaptability of proteins critical for survival. This project will support the training of high school, undergraduate, graduate, and post-graduate researchers on state-of-the-art techniques and instruments, helping the nation be prepared with qualified scientists who can solve problems at every level when we encounter our own extreme scenarios.This project, focused on protein dynamics inside living cells and organisms, has the goal of understanding how protein evolution optimizes flexibility, develops novel structure and function, and adapts proteins to subtle differences even between different cell types in a single organism. This will be accomplished through three distinct but related subprojects. A class of intrinsically disordered proteins with low charge/hydropathy ratio will be studied to determine if quinary structure and crowding in cells may be sufficient to induce structure. Using zebrafish as a model organism, heat shock chaperoning will be studied in vivo to determine how protein-chaperone interactions can be differentiated in different tissues. Extremophiles tune the native state fluctuations of enzymes to allow function under a wide range of temperatures, pressures, and other solvent variables. To elucidate how organisms tune the phase diagrams of their proteins to maximize function, experiments and simulations will be conducted on enzyme phosphoglycerate kinase from eight different mesophilic and extremophilic organisms covering a wide range of environments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

我们生活在一个环境变得越来越极端的世界里，但关于生物如何成功地适应极端条件，还有很多东西需要了解。脱水、高压、温度变化都是有弹性的生物体为了生存而能科普的变量，蛋白质扮演着特别重要的角色。这个研究项目着眼于一些蛋白质如何保护其他蛋白质时，温度上升太高的生存，几乎不能折叠的蛋白质如何在正确的环境中折叠，以及微生物如何生活在高压和高温下通过利用对生存至关重要的蛋白质的适应性来科普。该项目将支持对高中、本科、研究生和研究生研究人员进行最先进技术和仪器的培训，帮助国家准备好合格的科学家，当我们遇到自己的极端情况时，他们可以解决各个层面的问题。该项目专注于活细胞和生物体内的蛋白质动力学，目标是了解蛋白质进化如何优化灵活性，开发出新的结构和功能，并使蛋白质适应甚至单个生物体中不同细胞类型之间的细微差异。 这将通过三个不同但相关的次级项目来完成。将研究一类具有低电荷/亲水比的内在无序蛋白质，以确定五元结构和细胞中的拥挤是否足以诱导结构。使用斑马鱼作为模式生物，热休克伴侣将在体内研究，以确定如何蛋白质伴侣相互作用可以区分在不同的组织。极端微生物调节酶的天然状态波动，使其在广泛的温度，压力和其他溶剂变量下发挥作用。为了阐明生物如何调整其蛋白质的相图以最大限度地发挥功能，将对来自8种不同的中温和极端生物的磷酸甘油酸激酶进行实验和模拟，这些生物覆盖了广泛的环境。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

项目成果

Metastable States in the Hinge-Bending Landscape of an Enzyme in an Atomistic Cytoplasm Simulation

• DOI: 10.1021/acs.jpclett.3c03134
• 发表时间: 2024-01-22
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY LETTERS
• 影响因子: 5.7
• 作者: Samuel Russell，Premila P.;Maytin，Andrew K.;Gruebele，Martin
• 通讯作者: Gruebele，Martin

A Marcus-Type Inverted Region in the Translocation Kinetics of a Knotted Protein

打结蛋白易位动力学中的马库斯型反向区域

• DOI: 10.1021/acs.jpclett.3c02183
• 发表时间: 2023
• 期刊: The Journal of Physical Chemistry Letters
• 作者: Tripathi, Prabhat;Mehrafrooz, Behzad;Aksimentiev, Aleksei;Jackson, Sophie E.;Gruebele, Martin;Wanunu, Meni
• 通讯作者: Wanunu, Meni

TMAO: Protecting proteins from feeling the heat

TMAO：保护蛋白质免受热量影响

• DOI: 10.1016/j.bpj.2023.03.008
• 发表时间: 2023
• 期刊: Biophysical Journal
• 影响因子: 3.4
• 作者: Boob, Mayank M.;Sukenik, Shahar;Gruebele, Martin;Pogorelov, Taras V.
• 通讯作者: Pogorelov, Taras V.