Seeing and sensing single G protein-coupled receptors by atomic force microscopy. (April 2019)

• Record Type: Journal Article
• Authors: Sapra, K Tanuj; Spoerri, Patrizia M; Engel, Andreas; Alsteens, David; Müller, Daniel J
• Is Part Of: Current opinion in cell biology. Volume 57(2019)
• Page Start: 25
• Page End: 32
• Publication Date: 2019-04
• Subjects: Cells -- Periodicals; Cytology -- Periodicals; Cell Biology -- Periodicals; Biology -- Periodicals; Cells -- Periodicals; Review Literature -- Periodicals; Cell Biology; Biology; Cells; Review Literature; Cellules -- Périodiques; Cytologie -- Périodiques; Electronic journals; 571.6
• DOI: 10.1016/j.ceb.2018.10.006
• Languages: English
• ISSNs: 0955-0674

Abstract

Highlights: G protein-coupled receptors (GPCRs) regulate key physiological processes and are therefore important drug targets. Complementary approaches are required to obtain mechanistic insight into the structure-function relationship of GPCRs. AFM-based approaches allow various properties of GPCRs to be directly observed and quantified in physiological conditions. FD-based AFM can image single GPCRs at high-resolution and quantify the free-energy landscape of ligand-binding. AFM-based force spectroscopy interrogates the physical and chemical properties of GPCRs. Abstract : G protein-coupled receptors (GPCRs) relay extracellular information across cell membranes through a continuum of conformations that are not always captured in structures. Hence, complementary approaches are required to quantify the physical and chemical properties of the dynamic conformations linking to GPCR function. Atomic force microscopy (AFM)-based high-resolution imaging and force spectroscopy are unique methods to scrutinize GPCRs and to sense their interactions. Here, we exemplify recent AFM-based applications to directly observe the supramolecular assembly of GPCRs in native membranes, to measure the ligand-binding free-energy landscape, and how interactions modulate the structural properties of GPCRs. Common trends in GPCR function are beginning to emerge. We envision that technical developments in combining AFM with superresolution fluorescence imaging will provide insights into how cellular states modulate GPCRs and vice versa .