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

Guan Da Syu, Shih Chin Wang, Guangzhong Ma, Shuang Liu, Donna Pearce, Atish Prakash, Brandon Henson, Lien Chun Weng, Devlina Ghosh, Pedro Ramos, Daniel Eichinger, Ignacio Pino, Xinzhong Dong, Jie Xiao, Shaopeng Wang, Nongjian Tao, Kwang Sik Kim, Prashant J. Desai, Heng Zhu

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2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1997
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Syu, G. D., Wang, S. C., Ma, G., Liu, S., Pearce, D., Prakash, A., Henson, B., Weng, L. C., Ghosh, D., Ramos, P., Eichinger, D., Pino, I., Dong, X., Xiao, J., Wang, S., Tao, N., Kim, K. S., Desai, P. J., & Zhu, H. (2019). Development and application of a high-content virion display human GPCR array. Nature communications, 10(1), [1997]. https://doi.org/10.1038/s41467-019-09938-9