Distinct loops in arrestin differentially regulate ligand binding within the GPCR opsin

Nat Commun. 2012:3:995. doi: 10.1038/ncomms2000.


G-protein-coupled receptors are universally regulated by arrestin binding. Here we show that rod arrestin induces uptake of the agonist all-trans-retinal [corrected] in only half the population of phosphorylated opsin in the native membrane. Agonist uptake blocks subsequent entry of the inverse agonist 11-cis-retinal (that is, regeneration of rhodopsin), but regeneration is not blocked in the other half of aporeceptors. Environmentally sensitive fluorophores attached to arrestin reported that conformational changes in loop(V-VI) (N-domain) are coupled to the entry of agonist, while loop(XVIII-XIX) (C-domain) engages the aporeceptor even before agonist is added. The data are most consistent with a model in which each domain of arrestin engages its own aporeceptor, and the different binding preferences of the domains lead to asymmetric ligand binding by the aporeceptors. Such a mechanism would protect the rod cell in bright light by concurrently sequestering toxic all-trans-retinal [corrected] and allowing regeneration with 11-cis-retinal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrestin / chemistry
  • Arrestin / metabolism*
  • Cattle
  • Models, Molecular
  • Models, Theoretical
  • Opsins / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Retinaldehyde / metabolism
  • Spectrometry, Fluorescence


  • Arrestin
  • Opsins
  • Retinaldehyde