G-protein-coupled receptors (GPCRs) transduce physiological and sensory stimuli into appropriate cellular responses and mediate the actions of one-third of drugs. GPCR structural studies have revealed the general bases of receptor activation, signaling, drug action and allosteric modulation, but so far cover only 13% of nonolfactory receptors. We broadly surveyed the receptor modifications/engineering and methods used to produce all available GPCR crystal and cryo-electron microscopy (cryo-EM) structures, and present an interactive resource integrated in GPCRdb (http://www.gpcrdb.org) to assist users in designing constructs and browsing appropriate experimental conditions for structure studies.
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We acknowledge A. Tsolakou, D. Milic and K.S. Harpsøe for help with data annotation; I. Carson for development of the preliminary version of the Stabilising Mutation Analyser; and C.-J. Tsai for input on the description of cryo-EM construct engineering and experiments. This work was supported in part by the ERC (Starting Grant 639125 to D.E.G.), the Lundbeck Foundation (grants R163-2013-16327 and R218-2016-1266 to D.E.G.), the Swiss National Science Foundation (grant CRSII2_160805 to X.D.), the European Commisions Seventh Framework Program (FP7/2007-2013; grant 290605 (COFUND: PSI-FELLOW) to E.M.) and the COST Action CM1207 (‘GLISTEN’).
The authors declare no competing interests.
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Munk, C., Mutt, E., Isberg, V. et al. An online resource for GPCR structure determination and analysis. Nat Methods 16, 151–162 (2019). https://doi.org/10.1038/s41592-018-0302-x
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