Nature Communications (Jul 2021)

Selective targeting of ligand-dependent and -independent signaling by GPCR conformation-specific anti-US28 intrabodies

  • Timo W. M. De Groof,
  • Nick D. Bergkamp,
  • Raimond Heukers,
  • Truc Giap,
  • Maarten P. Bebelman,
  • Richard Goeij-de Haas,
  • Sander R. Piersma,
  • Connie R. Jimenez,
  • K. Christopher Garcia,
  • Hidde L. Ploegh,
  • Marco Siderius,
  • Martine J. Smit

DOI
https://doi.org/10.1038/s41467-021-24574-y
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 17

Abstract

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Various GPCRs display constitutive ligand-independent activity, but it remains unclear whether ligand-dependent and -independent conformations differ. Here the authors demonstrate the recognition and blocking of G protein recruitment of either the ligand-bound active, or the constitutively active apo-conformation of the viral GPCR US28 by different nanobodies that target similar intracellular loops of the receptor.