Arresting Developments in Biased Signaling

Trends Pharmacol Sci. 2020 Jun;41(6):387-389. doi: 10.1016/j.tips.2020.04.003. Epub 2020 Apr 30.

Abstract

The ability to design 'biased' drugs that selectively activate G protein-coupled receptor (GPCR) signaling pathways beneficial in treating a disease, while limiting their side effects, is of broad significance. Lee et al. move us a step closer to this important goal by identifying structural differences in the β1-adrenoceptor in complex with β-arrestin 1 versus a G protein-mimicking nanobody.

Keywords: G protein-coupled receptor; arrestin; cryo-EM.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomimetic Materials / chemistry
  • Humans
  • Models, Molecular
  • Molecular Targeted Therapy
  • Receptors, Adrenergic, beta-1 / chemistry
  • Receptors, Adrenergic, beta-1 / metabolism
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / drug effects
  • Single-Domain Antibodies / chemistry
  • beta-Arrestin 1 / chemistry*
  • beta-Arrestin 1 / metabolism

Substances

  • Receptors, Adrenergic, beta-1
  • Receptors, G-Protein-Coupled
  • Single-Domain Antibodies
  • beta-Arrestin 1