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Structural Insights into the Intrinsically Disordered GPCR C:Terminal Region, Major Actor in Arrestin:GPCR Interaction

Abstract : Arrestin-dependent pathways are a central component of G protein-coupled receptor (GPCRs) signaling. However, the molecular processes regulating arrestin binding are to be further illuminated, in particular with regard to the structural impact of GPCR C-terminal disordered regions. Here, we used an integrated biophysical strategy to describe the basal conformations of the C-terminal domains of three class A GPCRs, the vasopressin V2 receptor (V2R), the growth hormone secretagogue or ghrelin receptor type 1a (GHSR) and the β2-adernergic receptor (β2AR). By doing so, we revealed the presence of transient secondary structures in these regions that are potentially involved in the interaction with arrestin. These secondary structure elements differ from those described in the literature in interaction with arrestin. This suggests a mechanism where the secondary structure conformational preferences in the C-terminal regions of GPCRs could be a central feature for optimizing arrestins recognition
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https://hal.archives-ouvertes.fr/hal-03748408
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Submitted on : Tuesday, August 9, 2022 - 2:53:59 PM
Last modification on : Thursday, September 29, 2022 - 11:40:06 AM

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Myriam Guillien, Assia Mouhand, Aurelie Fournet, Amandine Gontier, Aleix Martí Navia, et al.. Structural Insights into the Intrinsically Disordered GPCR C:Terminal Region, Major Actor in Arrestin:GPCR Interaction. Biomolecules, MDPI, 2022, 12 (5), pp.617. ⟨10.3390/biom12050617⟩. ⟨hal-03748408⟩

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