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

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  • Martha E. Sommer

    (Institut für Medizinische Physik und Biophysik (CC2), Charité - Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.)

  • Klaus Peter Hofmann

    (Institut für Medizinische Physik und Biophysik (CC2), Charité - Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
    Zentrum für Biophysik und Bioinformatik, Humboldt-Universität zu Berlin, Invalidenstrasse 42, D-10115 Berlin, Germany.)

  • Martin Heck

    (Institut für Medizinische Physik und Biophysik (CC2), Charité - Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.)

Abstract

G-protein-coupled receptors are universally regulated by arrestin binding. Here we show that rod arrestin induces uptake of the agonist all-trans-retinol 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 loopV−VI (N-domain) are coupled to the entry of agonist, while loopXVIII−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-retinol and allowing regeneration with 11-cis-retinal.

Suggested Citation

  • Martha E. Sommer & Klaus Peter Hofmann & Martin Heck, 2012. "Distinct loops in arrestin differentially regulate ligand binding within the GPCR opsin," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
  • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2000
    DOI: 10.1038/ncomms2000
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    1. Junke Liu & Hengmin Tang & Chanjuan Xu & Shengnan Zhou & Xunying Zhu & Yuanyuan Li & Laurent Prézeau & Tao Xu & Jean-Philippe Pin & Philippe Rondard & Wei Ji & Jianfeng Liu, 2022. "Biased signaling due to oligomerization of the G protein-coupled platelet-activating factor receptor," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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