Tools for Probing Conformational Dynamics of Membrane Proteins

探测膜蛋白构象动力学的工具

• 批准号: 1902449
• 负责人: Nathaniel Traaseth
• 金额: $ 63.98万
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1902449&HistoricalAwards=false
• 关键词: Tools; Probing; Conformational; Dynamics; Membrane

Motion in biological molecules, termed dynamics, is a requirement for many biological functions including enzyme catalysis, molecular recognition, protein-protein interactions, and substrate transport. While progress has been made to determine structures of membrane proteins in discrete conformations using X-ray crystallography, much less is known about the role of protein dynamics in function. The overall goal of this project is to develop novel experimental methods to sensitively measure functionally-relevant motions required of membrane proteins. This project will involve high school, undergraduate, and graduate students in research, which will further disseminate knowledge in the interdisciplinary fields of biophysical chemistry, chemical biology, biochemistry, and structural biology and develop STEM workforce for bio-industry and -economy. This research will focus on the development and application of oriented sample nuclear magnetic resonance (OS-NMR) experiments. These methods will be applied to three membrane protein transporters of varying size and complexity to establish the feasibility of the methods to reveal functionally important membrane protein dynamics. This project will develop methods to overcome the major challenges in studying membrane protein dynamics. Specifically, biophysical insight into conformational motions of membrane proteins involved in substrate transport and spectroscopic innovation in the development of solid-state NMR techniques to probe dynamics will be developed. to improve undergraduate curricula and scientific training across the 50+ member institutions. This project is supported by the Molecular Biophysics Cluster of the Molecular and Cellular Biosciences Division in the Biological Sciences Directorate.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.

生物分子中的运动称为动力学，是包括酶催化、分子识别、蛋白质-蛋白质相互作用和底物运输在内的许多生物学功能所必需的。虽然用X射线结晶学确定离散构象中膜蛋白的结构已经取得了进展，但人们对蛋白质动力学在功能中的作用知之甚少。该项目的总体目标是开发新的实验方法来灵敏地测量膜蛋白所需的功能相关运动。该项目将吸引高中、本科生和研究生参与研究，进一步传播生物物理化学、化学生物学、生物化学和结构生物学等跨学科领域的知识，并为生物产业和经济发展STEM劳动力。本研究将侧重于定向样品核磁共振(OS-核磁共振)实验的开发和应用。这些方法将应用于三种不同大小和复杂程度的膜蛋白转运蛋白，以确定这些方法揭示功能重要的膜蛋白动力学的可行性。该项目将开发克服膜蛋白动力学研究中的主要挑战的方法。具体地说，将发展对参与底物运输的膜蛋白构象运动的生物物理见解，以及在开发固态核磁共振技术以探测动力学方面的光谱创新。改善50多个成员机构的本科课程和科学培训。该项目由生物科学局分子和细胞生物科学部的分子生物物理组支持。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为是值得支持的。

项目成果

Site-specific resolution of anionic residues in proteins using solid-state NMR spectroscopy

• DOI: 10.1007/s10858-020-00323-z
• 发表时间: 2020-06
• 期刊: Journal of Biomolecular NMR
• 影响因子: 2.7
• 作者: Jianping Li;Ampon Sae Her;N. Traaseth

Structural basis for inhibition of the drug efflux pump NorA from Staphylococcus aureus.

• DOI: 10.1038/s41589-022-00994-9
• 发表时间: 2022-07
• 期刊: Nature chemical biology
• 影响因子: 14.8
• 作者: Brawley DN;Sauer DB;Li J;Zheng X;Koide A;Jedhe GS;Suwatthee T;Song J;Liu Z;Arora PS;Koide S;Torres VJ;Wang DN;Traaseth NJ
• 通讯作者: Traaseth NJ

Asymmetric protonation of glutamate residues drives a preferred transport pathway in EmrE

• DOI: 10.1073/pnas.2110790118
• 发表时间: 2021-10-12
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Li, Jianping;Her, Ampon Sae;Traaseth, Nathaniel J.
• 通讯作者: Traaseth, Nathaniel J.