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

被引：13

作者：

Guillien, Myriam ^{[1
]}

Mouhand, Assia ^{[1
]}

Sagar, Amin ^{[1
]}

Fournet, Aurelie ^{[1
]}

Allemand, Frederic ^{[1
]}

Pereira, Glaecia A. N. ^{[2
]}

Thureau, Aurelien ^{[3
]}

Bernado, Pau ^{[1
]}

Baneres, Jean-Louis ^{[2
]}

Sibille, Nathalie ^{[1
]}

机构：

[1] Univ Montpellier, CNRS, Inserm, Ctr Biol Structurale CBS, Montpellier, France

[2] Univ Montpellier, CNRS, UMR 5247, ENSCM,Inst Biomol Max Mousseron IBMM, Montpellier, France

[3] LOrme Merisiers, Synchrotron SOLEI, HelioBio Sect, St Aubin BP 48, F-91190 Gif Sur Yvette, France

来源：

STRUCTURE | 2023年 / 31卷 / 11期

关键词：

INTRINSICALLY DISORDERED PROTEINS; MUSCARINIC ACETYLCHOLINE-RECEPTOR; SMALL-ANGLE SCATTERING; STRUCTURAL-CHARACTERIZATION; COUPLED RECEPTOR; BIOLOGICAL MACROMOLECULES; FLEXIBLE PROTEINS; UNFOLDED PROTEINS; DIPOLAR COUPLINGS; CHEMICAL-SHIFTS;

D O I：

10.1016/j.str.2023.08.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 beta 2-adernergic receptor (beta 2AR). Using phosphomimetic variants, we identified pre-formed secondary structure elements, or short linear motifs (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.

引用

页码：1394 / +

页数：21

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