Membrane Protein Structural Dynamics Lab

"Unraveling the Mysteries of Membrane Proteins and their dynamics"

Membrane proteins play a pivotal role in numerous cellular processes, including electrical excitability, cell-cell communication, ion transport, signaling pathways, and maintaining cellular homeostasis. Given that nearly two-thirds of approved drugs target membrane proteins, a comprehensive understanding of their functions is essential for advancing biomedical research and drug discovery. Unraveling the mechanistic details of membrane protein function requires an in-depth understanding of their structural dynamics across various functional states. Despite their significance, membrane proteins account for only ~3% of high-resolution structures in the Protein Data Bank. This scarcity is primarily due to challenges such as low expression levels, poor extraction efficiency, heterogeneity of membrane sources, and the inherent difficulty of producing well-ordered 3D crystals. One of the most significant obstacles is isolating membrane proteins from their native hydrophobic environment into a soluble, stable, and functional form that is amenable to structural and biophysical studies. Moreover, many high-resolution structural studies of membrane proteins are conducted under non-physiological conditions, such as in micellar environments. This approach often overlooks the critical influence of lipid-protein interactions on membrane protein structure and function. 

Recent advancements have enabled the study of various classes of membrane proteins in physiologically-relevant environments, using cutting-edge techniques such as site-directed fluorescence, nuclear magnetic resonance, high-speed atomic force microscopy, and cryo-electron microscopy. These approaches provide invaluable insights into the functionally-relevant conformational dynamics of membrane proteins, helping to validate existing structures and deepen our understanding of their roles. The growing interest in studying membrane proteins within native-like environments underscores the importance of this research field. As these complex and fascinating biological nanomachines continue to capture the attention of researchers, they hold great promise for advancing our knowledge of cellular mechanisms and facilitating the development of novel therapeutics.