Ionizable Residue Interactions in Tilted Transmembrane Helices

倾斜跨膜螺旋中的电离残基相互作用

• 批准号: 1327611
• 负责人: Roger Koeppe
• 金额: $ 68.45万
• 依托单位: University of Arkansas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1327611&HistoricalAwards=false
• 关键词: Ionizable; Residue; Interactions; Tilted; Transmembrane

This project addresses fundamental gaps in understanding the consequences of ionization and dynamics for the biological function of proteins in lipid-bilayer membranes. Solid-state magnetic resonance experiments will provide crucial benchmarks for the validation and integration of theory, computation and experiment. The experiments will employ a novel ?host? peptide design, in which minimal numbers of chemically distinct aromatic amino acid residues serve to position a tilted transmembrane helix near a ?tipping point? in lipid bilayer membranes. Within this context, the systematic incorporation of specific ionizable (potentially charged) ?guest? residues will provide important new insights concerning ionization behavior and protein-lipid molecular interactions that are essential for the biological functions of many classes of membrane proteins. In addition to fundamental insights about lipids and proteins, the project will advance the understanding of molecular mechanisms that may govern the functioning of potassium channels, acetylcholine receptors and integrins, among other membrane proteins. The project will extend longstanding commitments to community outreach and early involvement of undergraduate students in cutting-edge research. An overarching goal is the recruitment of new creative minds to lifelong careers dedicated to scientific discovery, while at the same time broadening the base for participation of non-traditional individuals and underrepresented groups in science. The project will contribute and enhance the undergraduate research opportunities?beginning at the freshman and sophomore levels. Additional efforts are devoted to the coordination of a statewide infrastructure for undergraduate research in Arkansas, a community Science Café and a protein virtual reality lab.

这个项目解决了在理解电离和动力学对脂质双层膜中蛋白质的生物功能的影响方面的根本空白。固体磁共振实验将为理论、计算和实验的验证和整合提供关键的基准。实验将采用一种新的？主持人？多肽设计，其中最少的化学上不同的芳香族氨基酸残基用于将倾斜的跨膜螺旋定位在临界点附近。在脂质双层膜中。在这种情况下，特定的可电离(可能带电的)？客体？残基将提供关于电离行为和蛋白质-脂质分子相互作用的重要新见解，这些行为和分子相互作用对于许多类别的膜蛋白的生物功能是必不可少的。除了对脂质和蛋白质的基本见解外，该项目还将促进对可能控制钾通道、乙酰胆碱受体和整合素等膜蛋白功能的分子机制的理解。该项目将延续长期以来对社区推广和本科生早期参与尖端研究的承诺。一个首要目标是在致力于科学发现的终身职业中招募新的创造性思维，同时扩大非传统个人和未被充分代表的群体参与科学的基础。该项目将有助于和增加本科生的研究机会？？从一年级和二年级开始。此外，还致力于协调阿肯色州本科生研究的全州基础设施、社区科学咖啡馆和蛋白质虚拟现实实验室。