GPCR structural characterization by NMR spectroscopy in solution
In the human proteome, 826 G-protein-coupled receptors (GPCRs) interact with extracellular stimuli to initiate cascades of intracellular signaling. Determining conformational dynamics and intermolecular interactions are key to understand GPCR function as a basis for drug design. X-ray crystallograph...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2022-08-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022106 |
| _version_ | 1797635382916939776 |
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| author | Yang Lingyun Liu Dongsheng Wüthrich Kurt |
| author_facet | Yang Lingyun Liu Dongsheng Wüthrich Kurt |
| author_sort | Yang Lingyun |
| collection | DOAJ |
| description | In the human proteome, 826 G-protein-coupled receptors (GPCRs) interact with extracellular stimuli to initiate cascades of intracellular signaling. Determining conformational dynamics and intermolecular interactions are key to understand GPCR function as a basis for drug design. X-ray crystallography and cryo-electron microscopy (cryo-EM) contribute molecular architectures of GPCRs and GPCR-signaling complexes. NMR spectroscopy is complementary by providing information on the dynamics of GPCR structures at physiological temperature. In this review, several NMR approaches in use to probe GPCR dynamics and intermolecular interactions are discussed. The topics include uniform stable-isotope labeling, amino acid residue-selective stable-isotope labeling, site-specific labeling by genetic engineering, the introduction of <sup>19</sup>F-NMR probes, and the use of paramagnetic nitroxide spin labels. The unique information provided by NMR spectroscopy contributes to our understanding of GPCR biology and thus adds to the foundations for rational drug design. |
| first_indexed | 2024-03-11T12:21:19Z |
| format | Article |
| id | doaj.art-f43a37df32454a458f60e4229eb6acb6 |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:21:19Z |
| publishDate | 2022-08-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-f43a37df32454a458f60e4229eb6acb62023-11-07T01:01:25ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-08-01541207121210.3724/abbs.202210620d259ccGPCR structural characterization by NMR spectroscopy in solutionYang Lingyun0Liu Dongsheng1Wüthrich Kurt2["iHuman Institute, ShanghaiTech University, Shanghai 201210, China"]["iHuman Institute, ShanghaiTech University, Shanghai 201210, China"]["iHuman Institute, ShanghaiTech University, Shanghai 201210, China","Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA 92037, USA","Institute of Molecular Biology and Biophysics, ETH Zürich, Otto-Stern-Weg 5, 8093 Zürich, Switzerland"]In the human proteome, 826 G-protein-coupled receptors (GPCRs) interact with extracellular stimuli to initiate cascades of intracellular signaling. Determining conformational dynamics and intermolecular interactions are key to understand GPCR function as a basis for drug design. X-ray crystallography and cryo-electron microscopy (cryo-EM) contribute molecular architectures of GPCRs and GPCR-signaling complexes. NMR spectroscopy is complementary by providing information on the dynamics of GPCR structures at physiological temperature. In this review, several NMR approaches in use to probe GPCR dynamics and intermolecular interactions are discussed. The topics include uniform stable-isotope labeling, amino acid residue-selective stable-isotope labeling, site-specific labeling by genetic engineering, the introduction of <sup>19</sup>F-NMR probes, and the use of paramagnetic nitroxide spin labels. The unique information provided by NMR spectroscopy contributes to our understanding of GPCR biology and thus adds to the foundations for rational drug design. https://www.sciengine.com/doi/10.3724/abbs.2022106G protein-coupled receptor dynamicsstable-isotope labelingfluorine-19 NMRGPCR biologydrug development |
| spellingShingle | Yang Lingyun Liu Dongsheng Wüthrich Kurt GPCR structural characterization by NMR spectroscopy in solution Acta Biochimica et Biophysica Sinica G protein-coupled receptor dynamics stable-isotope labeling fluorine-19 NMR GPCR biology drug development |
| title | GPCR structural characterization by NMR spectroscopy in solution |
| title_full | GPCR structural characterization by NMR spectroscopy in solution |
| title_fullStr | GPCR structural characterization by NMR spectroscopy in solution |
| title_full_unstemmed | GPCR structural characterization by NMR spectroscopy in solution |
| title_short | GPCR structural characterization by NMR spectroscopy in solution |
| title_sort | gpcr structural characterization by nmr spectroscopy in solution |
| topic | G protein-coupled receptor dynamics stable-isotope labeling fluorine-19 NMR GPCR biology drug development |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022106 |
| work_keys_str_mv | AT yanglingyun gpcrstructuralcharacterizationbynmrspectroscopyinsolution AT liudongsheng gpcrstructuralcharacterizationbynmrspectroscopyinsolution AT wuthrichkurt gpcrstructuralcharacterizationbynmrspectroscopyinsolution |