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Article Dans Une Revue Structure Année : 2023

Phosphorylation motif dictates GPCR C-terminal domain conformation and arrestin interaction

Le motif de phosphorylation dicte la conformation du domaine C-terminal des RCPG et leur interaction avec l'arrestine

Résumé

Arrestin dependent G protein-coupled receptor (GPCR) signaling pathway is regulated by the phosphorylation state of GPCR’s C-terminal domain, but the molecular bases of arrestin:receptor interaction are to be further illuminated. Here we investigated the impact of phosphorylation on the conformational features of the C-terminal region from three rhodopsin-like GPCRs, the vasopressin V2 Receptor (V2R), the Growth Hormone Secretagogue or ghrelin Receptor type 1a (GHSR) and the β2-Adernergic Receptor (β2AR). Using phosphomimetic variants, we identified pre-formed secondary structure elements, or short linear motif (SLiMs), that undergo specific conformational transitions upon phosphorylation. Of importance, such conformational transitions appear to favor arrestin-2 binding. Hence, our results suggest a model in which the phosphorylation-dependent structuration of the GPCR C-terminal regions would modulate arrestin binding, and therefore signaling outcomes in arrestin dependent pathways.
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Dates et versions

hal-04235502 , version 1 (10-10-2023)

Identifiants

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Myriam Guillien, Assia Mouhand, Amin Sagar, Aurélie Fournet, Frédéric Allemand, et al.. Phosphorylation motif dictates GPCR C-terminal domain conformation and arrestin interaction. Structure, 2023, 31 (11), pp.1394-1406.e7. ⟨10.1016/j.str.2023.08.011⟩. ⟨hal-04235502⟩
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