IntroductionG Protein-Coupled Receptors (GPCRs) are transmembrane (TM) proteins that span the cell membrane seven times, and contain intracellular and extracellular domains comprised of connecting loops as well as terminal extension sequences. GPCRs bind ligands within their transmembrane and/or extracellular domains. Ligand binding elicits conformational changes that initiate downstream intracellular signaling events through arrestins and G proteins ( Figure 1; Katritch et al., 2013). GPCRs play central roles in many physiological processes from sensory to neurological, cardiovascular, endocrine, and reproductive functions. GPCRs represent one of the largest gene families in the human genome, encoding approximately 800 unique proteins (Fredriksson et al., 2003). GPCRs' unique structure and cell surface location make them ideal targets for various drug therapies, assuring interest from the pharmaceutical and clinical medicine communities (Vischer et al., 2011). It is estimated that roughly 40% of the pharmaceuticals currently marketed, target GPCRs (Vischer et al., 2011). BI-167107, bovine Gs;Rasmussen et al., 2011) Urbana-Champaign (Humphreys et al., 1996). This image was made with Visual Molecular Dynamics (VMD). VMD is developed with NIH support by the Theoretical and Computational Biophysics group at the Beckman Institute, University of Illinois atThe elucidation of x-ray crystallographic structures of GPCRs has been monumental to the research in understanding the function and conformational flexibility of GPCRs (Costanzi 2014;Venkatakrishnan et al., 2014). Understanding how ligand binding alters the structure and function of GPCRs to mediate signaling has undergone an expansion in recent years (Katritch et al., 2013). Concepts such as ligands acting as functionally selective biased agonists to elicit a specific subset of signaling responses are now at the forefront of GPCR research (Andresen 2011). Development of allosteric ligands extends the repertoire of GPCR regulators (Smith 2010). GPCRs were originally considered to be monomeric, but increasing evidence indicates that they can form dimers and oligomers as well (Ferre et al., 2014 Piscitelli et al., 2015), has been described as a "crystallization boom" (Costanzi 2014), with rapid growth emerging due to recent technological advances in both crystallization and structure detection. The availability of growing numbers of experimentally-determined GPCR structures, as well as improved homology-modeling of unknown target proteins based on a wider field of experimentally determined GPCR template structures, allows visual representation of GPCRs to be built upon the basis of known or modeled three-dimensional structures. Nevertheless, several challenges to accurate communication of GPCR structure remain.The goal of this paper is to provide strategies to address common visual representation challenges for GPCRs, and to identify errors that may arise from an incomplete understanding of GPCR structure. GPCRs comprise a subclass of the alpha-helical membrane p...