An online resource for GPCR structure determination and analysis


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 ( to assist users in designing constructs and browsing appropriate experimental conditions for structure studies.

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Fig. 1: Progress and space yet to be covered in the structural characterization of GPCRs.
Fig. 2: Snapshots from the online resource for GPCR crystallography and cryo-EM.
Fig. 3: Common GPCR structure construct modifications and alignment of constructs for structural determination.
Fig. 4: Active-state GPCR structures, including complexed proteins and cryo-EM structures.
Fig. 5: Mapping of fusion proteins and fusion sites in all GPCR structure constructs.
Fig. 6: Substitution frequencies, structural mapping and rationale for stabilizing mutations.
Fig. 7: Key expression, purification and structure determination methods and reagents.


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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’).

Author information




C.M., D.E.G., J.M.B. and T.F. made the construct analyses and figures; C.M. and V.I. developed the online resources; E.M. and C.M. annotated and analyzed published experimental data; L.F.N. conducted the mutagenesis experiments; M.A.H. and R.C.S. provided critical input on the project, manuscript writing and data analysis; X.D. and D.E.G. drafted the paper; all authors commented on the drafted manuscript; D.E.G. and X.D. designed the project; and D.E.G. managed the project.

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Correspondence to Christian Munk or David E. Gloriam.

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Supplementary Note 1 and Supplementary Tables 1–5

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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).

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