Development and application of a high-content virion display human GPCR array

Nat Commun. 2019 Apr 30;10(1):1997. doi: 10.1038/s41467-019-09938-9.


Human G protein-coupled receptors (GPCRs) respond to various ligands and stimuli. However, GPCRs rely on membrane for proper folding, making their biochemical properties difficult to study. By displaying GPCRs in viral envelopes, we fabricated a Virion Display (VirD) array containing 315 non-olfactory human GPCRs for functional characterization. Using this array, we found that 10 of 20 anti-GPCR mAbs were ultra-specific. We further demonstrated that those failed in the mAb assays could recognize their canonical ligands, suggesting proper folding. Next, using two peptide ligands on the VirD-GPCR array, we identified expected interactions and novel interactions. Finally, we screened the array with group B Streptococcus, a major cause of neonatal meningitis, and demonstrated that inhibition of a newly identified target, CysLTR1, reduced bacterial penetration both in vitro and in vivo. We believe that the VirD-GPCR array holds great potential for high-throughput screening for small molecule drugs, affinity reagents, and ligand deorphanization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Chlorocebus aethiops
  • Fluorescent Antibody Technique
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Proteomics / methods
  • Receptors, G-Protein-Coupled / metabolism*
  • Streptococcus / metabolism
  • Vero Cells
  • Virion / metabolism*
  • Virology / methods


  • Receptors, G-Protein-Coupled