A molecular dynamics study of membrane positioning for 7-transmembrane RGS proteins to modulate G-protein-mediated signaling in plants

A molecular dynamics study of membrane positioning for 7-transmembrane RGS proteins to modulate G-protein-mediated signaling in plants

Protein phosphorylation regulates G protein signaling in plants. AtRGS1 primarily modulates AtGPA1, the canonical Gα subunit in the heterotrimeric G protein complex. AtRGS1 possesses both a seven-transmembrane (7TM) domain connected to a cytoplasmic Regulator of G Protein Signaling domain (RGS box d...

Full description

Saved in:
Bibliographic Details
Main Authors: Celio Cabral Oliveira, Eduardo Bassi Simoni, Mariana Abrahão Bueno Morais, Elizabeth Pacheco Batista Fontes, Pedro A. Braga dos Reis, Daisuke Urano, Alan M. Jones
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Computational and Structural Biotechnology Journal
Subjects:
Arabidopsis
Regulator of G protein signaling (RGS)
Linker domain
Heterotrimeric G protein
Molecular dynamics
Protein evolution
Online Access:http://www.sciencedirect.com/science/article/pii/S2001037025001333
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Protein phosphorylation regulates G protein signaling in plants. AtRGS1 primarily modulates AtGPA1, the canonical Gα subunit in the heterotrimeric G protein complex. AtRGS1 possesses both a seven-transmembrane (7TM) domain connected to a cytoplasmic Regulator of G Protein Signaling domain (RGS box domain) by a flexible linker region. This study presents the novel function of a highly conserved, known phosphorylation site, Ser278, within this linker region utilizing molecular dynamics (MD) simulations with in vivo experimental validation. We show that phosphorylation at Ser278 is crucial for establishing specific AtRGS1 interactions with AtGPA1, primarily by stabilizing the positioning and orientation of the RGS domain within the membrane. Phosphorylation at Ser278 enhances the formation of stable hydrogen bonds between phosphorylated Ser278 and conserved residues within the RGS box domain, influencing the flexibility of RGS domain mobility and thus modulating its interface to AtGPA1. Consistent with the MD simulations, in vivo assays demonstrated that this phosphorylation reduced the binding of AtRGS1 to AtGPA1 and conferred changes in physiology. Specifically, the non-phosphorylation mutation of Ser278 decreased both plant immune responses and AtRGS1 endocytosis evoked by the bacterial effector, flg22. MD simulations and sequence analysis of diverse plant 7TM-RGS proteins suggest conservation of this mechanism across land plants, emphasizing the critical role of this previously overlooked linker region.
ISSN:2001-0370

Similar Items