Mechanisms of Protein Protection by Desiccation-tolerance Molecules

耐干燥分子保护蛋白质的机制

• 批准号: 2203505
• 负责人: Gary Pielak
• 金额: $ 49.5万
• 依托单位: University of North Carolina at Chapel Hill
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2203505&HistoricalAwards=false
• 关键词: Mechanisms; Protein; Protection; Desiccation; tolerance

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Gary J. Pielak from the University of North Carolina at Chapel Hill to investigate mechanisms of protein protection used by large and small desiccation tolerance molecules. Organisms selected to survive desiccation do so by making protective molecules, but the mechanisms of protection are mostly unknown. From a practical perspective, understanding dehydration protection will improve biomanufacturing processes and bio-based products, such as biologic drugs and industrial enzymes. These studies will provide graduate and undergraduate students with specialized training in protein chemistry and physical biochemistry, which are useful skills for basic and industrial research. The PI will also work with the Carolina Covenant, a program that helps low-income UNC students graduate debt-free, to train students interested in chemistry research.The four main ideas proposed to explain desiccation protection — water retention, vitrification, water replacement and molecular shield hypotheses — will be tested by using a combination of protein engineering, nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy and rheometry. The most common natural protective small molecule is the nonreducing disaccharide, trehalose, but there are also several classes of protective disordered proteins. The most well-studied members are the Late Embryogenesis Abundant (LEA) proteins, which were discovered in plants but are also found in animals. The most recently discovered class of protective proteins — Cytosolic Abundant Heat Soluble (CAHS) proteins — are unique to tardigrades. CAHS proteins are remarkable not only because they protect other proteins and enzymes but also because they form protective gels. This project will compare and contrast each of these types of protective molecules to better understand how their structures contribute to the survival of organisms under dehydrating conditions.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.

凭借该奖项，化学部的生命过程化学项目正在资助北卡罗来纳大学教堂山分校的 Gary J. Pielak 博士研究大小干燥耐受分子所使用的蛋白质保护机制。选择在干燥环境下生存的生物体是通过制造保护性分子来实现的，但保护机制大多未知。从实践的角度来看，了解脱水保护将改善生物制造工艺和生物基产品，例如生物药物和工业酶。这些研究将为研究生和本科生提供蛋白质化学和物理生物化学方面的专门培训，这些技能对于基础和工业研究来说是有用的技能。 PI 还将与 Carolina Covenant 合作，这是一个帮助北卡罗来纳大学低收入学生无负债毕业的项目，培训对化学研究感兴趣的学生。提出的四个主要解释干燥保护的想法——保水、玻璃化、水替代和分子屏蔽假设——将通过结合使用蛋白质工程、核磁共振光谱、傅里叶变换红外光谱和流变测量来进行测试。最常见的天然保护性小分子是非还原性二糖、海藻糖，但也有几类保护性无序蛋白质。研究最深入的成员是胚胎发生晚期丰富 (LEA) 蛋白，该蛋白在植物中发现，但也在动物中发现。最近发现的一类保护性蛋白质——胞质丰富的热溶性（CAHS）蛋白质——是缓步动物所独有的。 CAHS 蛋白质之所以引人注目，不仅因为它们可以保护其他蛋白质和酶，还因为它们可以形成保护凝胶。该项目将比较和对比每种类型的保护分子，以更好地了解它们的结构如何有助于有机体在脱水条件下的生存。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

How Sugars Protect Dry Protein Structure.

• DOI: 10.1021/acs.biochem.2c00692
• 发表时间: 2023-03-07
• 期刊: BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Brom, Julia A.;Petrikis, Ruta G.;Pielak, Gary J.
• 通讯作者: Pielak, Gary J.