Tools for Probing Conformational Dynamics of Membrane Proteins

New York University, New York NY

Investigators

Abstract

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.