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PMID: 22871814 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature communications ·Vol. 3 ·2012-00-00 ·Pages 995

Sommer ME, Hofmann KP, Heck M

Abstract

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.

MeSH Terms
Animals Arrestin/chemistry,metabolism Cattle Models, Molecular Models, Theoretical Opsins/metabolism Protein Binding Protein Structure, Secondary Retinaldehyde/metabolism Spectrometry, Fluorescence
Chemicals
Arrestin Opsins Retinaldehyde
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sommer Martha E
Institut für Medizinische Physik und Biophysik (CC2), Charité - Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany. martha.sommer@charite.de
Hofmann Klaus Peter
Heck Martin
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms2000
Email
martha.sommer@charite.de
Published
2012-00-00
Pages
995
Language
English
Region
England
NLM ID
101528555
PMCID
PMC3455371
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1038/ncomms2000 PMC Full Text View journal details
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