G protein-coupled receptors (GPCRs) transduce physiological and sensory stimuli into appropriate cellular responses and mediate the actions of one-third of drugs. Structures of GPCRs are therefore extremely valuable for understanding basic receptor function and rational drug design. Today, 310 structures of 59 distinct receptors (https://gpcrdb.org/structure/statistics) have revealed the general bases of receptor activation, signalling, drug action and allosteric modulation. However, there are still no structures for the vast majority – 85% – of the 398 non-olfactory GPCRs and for 52% structure models can only be based on low-homology templates.
To accelerate the determination of GPCR structures and to help assess the quality of the available templates based on the modifications and methods, a recent article in Nature Methods presents “An Online Resource for GPCR Structure Determination and Analysis” . This surveyes the construct engineering and experimental methods and reagens used to produce all available GPCR crystal and cryo-EM structures. Furthermore, it describes and interactive resource integrated in GPCRdb (www.gpcrdb.org) to assist users in designing new constructs and browsing appropriate experimental conditions for structure studies.
(1) Munk C et al. (2019). An online resource for GPCR structure determination and analysis. J Med Chem, doi:10.1038/s41592-018-0302-x. [PMID:30664776]