Structural plasticity of arrestin-G protein coupled receptor complexes as a molecular determinant of signaling.

Autor: Felline A; Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, via Campi 103, 41125 Modena, Italy., Bellucci L; NEST, Istituto Nanoscienze-CNR, Piazza San Silvestro 12, 56127 Pisa, Italy., Vezzi V; Istituto Superiore di Sanità, V.le Regina Elena, 299 00161 Roma, Italy., Ambrosio C; Istituto Superiore di Sanità, V.le Regina Elena, 299 00161 Roma, Italy., Cotecchia S; Dipartimento di Bioscienze, Biotecnologie e Ambiente, Università di Bari, via Orabona 4, 70125 Bari, Italy., Fanelli F; Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, via Campi 103, 41125 Modena, Italy. Electronic address: fanelli@unimo.it.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Dec; Vol. 283 (Pt 1), pp. 137217. Date of Electronic Publication: 2024 Nov 07.
DOI: 10.1016/j.ijbiomac.2024.137217
Abstrakt: G protein coupled receptors (GPCRs) are critically regulated by arrestins. In this study, high-resolution data was combined with molecular dynamics simulations to infer the determinants of β-arrestin 1 (βarr1)-GPCR coupling, using the V2 vasopressin receptor (V2R) as a model system. The study highlighted the extremely high plasticity of βarr1-GPCR complexes, dependent on receptor type, state, and membrane environment. The multiple functions of receptor-bound βarr1 are likely determined by the interplay of intrinsic flexibility and collective motions both as a bi-domain protein and as a whole. The two major collective motions of the whole βarr1, consisting in rotation parallel to the membrane plane and inclination with respect to the receptor main axis, are distinctly linked to the two intermolecular interfaces involved in tail and core interactions. The intermolecular dynamic coupling between βarr1 and V2R depends on the allosteric effect of the agonist arginine-vasopressin (AVP). In the absence of AVP the dynamic coupling concerns only tail interactions, while in the presence of AVP it involves both tail and core interactions. This suggests that constitutive and agonist-induced arrestin-receptor dynamic coupling is linked to distinct arrestin functions.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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