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Annual Review of Biophysics

Volume 53, 2024

Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function

Abstract

Integral membrane proteins (IMPs) play central roles in cellular physiology and represent the majority of known drug targets. Single-molecule fluorescence and fluorescence resonance energy transfer (FRET) methods have recently emerged as valuable tools for investigating structure–function relationships in IMPs. This review focuses on the practical foundations required for examining polytopic IMP function using single-molecule FRET (smFRET) and provides an overview of the technical and conceptual frameworks emerging from this area of investigation. In this context, we highlight the utility of smFRET methods to reveal transient conformational states critical to IMP function and the use of smFRET data to guide structural and drug mechanism-of-action investigations. We also identify frontiers where progress is likely to be paramount to advancing the field.

Keyword(s): fluorescence resonance energy transfer, genetic code expansion, integral membrane proteins, intrinsically dynamic systems, metastable energy landscape, single-molecule imaging
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/content/journals/10.1146/annurev-biophys-070323-024308
2024-07-16
2025-04-29
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Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function
Annual Review of Biophysics 53, 427 (2024); https://doi.org/10.1146/annurev-biophys-070323-024308
/content/journals/10.1146/annurev-biophys-070323-024308
/content/journals/10.1146/annurev-biophys-070323-024308
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