GPCR Organization
The largest family of membrane proteins, G protein-coupled receptors (GPCRs), has enormous pharmacological importance and many efforts are underway to better target this ubiquitous class of membrane proteins. One intriguing hypothesis is that some GPCRs form dimeric complexes that can regulate signaling outcomes. Our lab has resolved the dimerization state of rhodopsin and discovered a novel dimerization interface of human cone opsins. We have also resolved the dimerization states of representative members of class A, B and C GPCRs and made quantitative comparisons with single molecule FRET methods. We continue to work on GPCR homo and heterodimerization, especially as it relates to cell signaling in cancer.
Asher, W. B.; Geggier, P.; Holsey, M. D.; Gilmore, G. T.; Pati, A. K.; Meszaros, J.; Terry, D. S.; Mathiasen, S.; Kaliszewski, M. J.; McCauley, M. D.; et al. Single-molecule FRET imaging of GPCR dimers in living cells. Nat Methods 2021, 18 (4), 397-405. DOI: https://doi.org/10.1038/s41592-021-01081-y
Mallory, D. P.; Gutierrez, E.; Pinkevitch, M.; Klinginsmith, C.; Comar, W. D.; Roushar, F. J.; Schlebach, J. P.; Smith, A. W.; Jastrzebska, B. The Retinitis Pigmentosa-Linked Mutations in Transmembrane Helix 5 of Rhodopsin Disrupt Cellular Trafficking Regardless of Oligomerization State. Biochemistry 2018, 57 (35), 5188-5201. DOI: https://doi.org/10.1021/acs.biochem.8b00403
Jastrzebska, B.; Comar, W. D.; Kaliszewski, M. J.; Skinner, K. C.; Torcasio, M. H.; Esway, A. S.; Jin, H.; Palczewski, K.; Smith, A. W. A G Protein-Coupled Receptor Dimerization Interface in Human Cone Opsins. Biochemistry 2017, 56 (1), 61-72. DOI: https://doi.org/10.1021/acs.biochem.6b00877.
Comar, W. D.; Schubert, S. M.; Jastrzebska, B.; Palczewski, K.; Smith, A. W. Time-Resolved Fluorescence Spectroscopy Measures Clustering and Mobility of a G Protein-Coupled Receptor Opsin in Live Cell Membranes. J Am Chem Soc 2014, 136 (23), 8342-8349. DOI: https://doi.org/10.1021/ja501948w