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How do cytosolic proteins interact with lipid droplets? A bio-physical chemical approach to an unresolved biological problem.

胞浆蛋白如何与脂滴相互作用？

基本信息

批准号：
1808281
负责人：
Edgar Kooijman
金额：
$ 42.3万
依托单位：
Kent State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1808281&HistoricalAwards=false
关键词：
How do cytosolic proteins interact

项目摘要

The Chemistry of Life Processes Program in the Chemistry Division has funded Dr. Edgar E. Kooijman and Dr. Elizabeth K. Mann, at Kent State University, to unravel how proteins interact with the surface of lipid droplets. Lipid droplets are fat particles that are crucial for supplying and regulating energy within the cell, and are involved in a whole host of other cellular processes. This research focuses on how proteins in cells are targeted to and bind to the surface of these lipid droplets, where they regulate droplet structure and function. While much is known about how proteins bind to the lipid membrane that encloses complex cells, essentially nothing is known for lipid droplets. Using model proteins, this research is determining the interactions responsible for the binding of lipid droplet proteins. As such, this work is transforming understanding of the structure and function of lipid droplets. Graduate, undergraduate, and high school students are working together in a highly interdisciplinary environment. Additionally, this work is resulting in meaningful educational experiences for low socioeconomic and minority background students, with the goal of increased STEM degrees among diverse students.This research project is an investigation of how cytosolic lipid droplet binding proteins interact with the surface of these crucial, but poorly understood, organelles. Elucidation of the exact protein-lipid interactions is transforming the understanding of lipid droplet biology as results are providing insight not only on lipid metabolism but also on the diverse functions of lipid droplets. Perilipins, and specifically, perilipin 3, are serving as the model protein(s) to characterize exactly how different protein domains are involved in protein-lipid interaction at the lipid droplet interface. Special attention is being given to the amphipathic alpha-helix bundle domain found in many proteins that interact with neutral lipid particles. A diverse array of experimental tools is being used, including a PI-built monolayer trough, a PI-built oil drop tensiometer, site directed mutagenesis, and protein expression and purification, supplemented by in vivo localization studies. This work thus provides key insights into the structure and physiological function of lipid droplets.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.

化学学部的生命过程化学项目资助了肯特州立大学的Edgar E. Kooijman博士和Elizabeth K. Mann博士，以揭示蛋白质如何与脂滴表面相互作用。脂滴是一种脂肪颗粒，对细胞内的能量供应和调节至关重要，并参与了许多其他细胞过程。这项研究的重点是细胞中的蛋白质如何靶向并结合到这些脂滴的表面，在那里它们调节脂滴的结构和功能。虽然人们对蛋白质如何与包裹复杂细胞的脂质膜结合已经了解得很多，但对脂滴的情况基本上一无所知。利用模型蛋白，本研究确定了脂滴蛋白结合的相互作用。因此，这项工作正在改变对脂滴结构和功能的理解。研究生，本科生和高中生在一个高度跨学科的环境中一起工作。此外，这项工作为低社会经济和少数民族背景的学生带来了有意义的教育经验，目标是在不同的学生中增加STEM学位。本研究项目是对细胞质脂滴结合蛋白如何与这些重要但鲜为人知的细胞器表面相互作用的研究。准确的蛋白质-脂质相互作用的阐明正在改变对脂滴生物学的理解，因为结果不仅提供了脂代谢的见解，而且还提供了脂滴的各种功能。perilipin，特别是perilipin 3，被用作模型蛋白来准确表征不同的蛋白结构域如何参与脂滴界面上的蛋白-脂相互作用。特别注意的是在许多与中性脂质颗粒相互作用的蛋白质中发现的两亲性α -螺旋束结构域。正在使用多种实验工具，包括pi构建的单层槽，pi构建的油滴张力计，定点诱变，蛋白质表达和纯化，并辅以体内定位研究。因此，这项工作为脂滴的结构和生理功能提供了关键的见解。该奖项反映了美国国家科学基金会的法定使命，并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，被认为值得支持。