Biophysics of protein interactions on membrane surfaces

膜表面蛋白质相互作用的生物物理学

• 批准号: 1712740
• 负责人: Kalina Hristova
• 金额: $ 90万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1712740&HistoricalAwards=false
• 关键词: Biophysics; protein; interactions; membrane; surfaces

Many critical cellular functions are regulated by protein interactions in the plasma membrane. Quantitative measurements of protein interactions in membranes, however, are challenging to perform due to many limitations of current experimental methodologies. This work will advance quantitative biophysical tools and will provide the broad scientific community with better methods to study membrane protein folding, structure, and function. Ultimately, improvement in methods will lead to discoveries that help reveal the role of interactions on membrane surfaces and their biological function in cells. The project will support training and the professional development of graduate and undergraduate students at Johns Hopkins University. This project will also provide educational and training opportunities for young scientists from diverse backgrounds and for students from Baltimore City Schools. The goal of the research is to develop a general biophysical methodology that can uncover the strength and the mechanism of interactions that occur on the membrane surface, between membrane receptors and cytoplasmic proteins. These interactions have profound biological significance, as they trigger the propagation of biochemical signals from the plasma membrane to the cytoplasm. They are very common in biology, as membrane receptors are known to interact with multiple cytoplasmic partners. Yet, these processes are complex and poorly understood. The strength of the interactions between membrane receptors and cytoplasmic proteins can depend on the association state of the receptor. The soluble partners, in turn, can modulate the interactions of the receptors in the membrane. Quantitative details, as well as biophysical methods that can yield such quantitative details, are lacking. The protocols that will be developed in this project will fill a large gap in methodology. They can be used for any combination of a membrane protein and soluble protein, and can reveal many new interactions. This project is jointly supported by the Molecular Biophysics Cluster of the Molecular and Cellular Biosciences Division in the Directorate for Biological Sciences and by the Biomaterials Program of the Division of Materials Research in the Directorate for Physical and Mathematical Sciences.

许多重要的细胞功能是由质膜中的蛋白质相互作用调节的。然而，由于目前实验方法的许多限制，膜中蛋白质相互作用的定量测量是具有挑战性的。这项工作将推进定量生物物理工具，并将为广大科学界提供更好的方法来研究膜蛋白折叠，结构和功能。最终，方法的改进将有助于揭示膜表面相互作用的作用及其在细胞中的生物学功能。该项目将支持约翰霍普金斯大学研究生和本科生的培训和专业发展。 该项目还将为来自不同背景的青年科学家和来自巴尔的摩城市学校的学生提供教育和培训机会。该研究的目标是开发一种通用的生物物理方法，可以揭示膜表面上发生的膜受体和细胞质蛋白之间相互作用的强度和机制。 这些相互作用具有深刻的生物学意义，因为它们触发了生物化学信号从质膜到细胞质的传播。它们在生物学中非常常见，因为已知膜受体与多个细胞质伴侣相互作用。然而，这些过程是复杂的，人们对它们的了解很少。膜受体和细胞质蛋白之间的相互作用的强度可以取决于受体的缔合状态。可溶性伴侣反过来可以调节膜中受体的相互作用。缺乏定量的细节，以及生物物理方法，可以产生这样的定量细节。将在本项目中开发的协议将填补方法上的一个巨大空白。它们可以用于膜蛋白和可溶性蛋白的任何组合，并且可以揭示许多新的相互作用。该项目由生物科学理事会分子和细胞生物科学部的分子生物物理学小组和物理和数学科学理事会材料研究部的生物材料计划共同支持。

项目成果

Quantifying the strength of heterointeractions among receptor tyrosine kinases from different subfamilies: Implications for cell signaling

量化不同亚家族受体酪氨酸激酶之间异质相互作用的强度：对细胞信号传导的影响

• DOI: 10.1074/jbc.ra120.013639
• 发表时间: 2020
• 期刊: Journal of Biological Chemistry
• 影响因子: 4.8
• 作者: Paul, Michael D.;Grubb, Hana N.;Hristova, Kalina
• 通讯作者: Hristova, Kalina

EGFR forms ligand-independent oligomers that are distinct from the active state

• DOI: 10.1074/jbc.ra120.012852
• 发表时间: 2020-09-18
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Byrne, Patrick O.;Hristova, Kalina;Leahy, Daniel J.
• 通讯作者: Leahy, Daniel J.