Distinct phosphorylation sites in a prototypical GPCR differently orchestrate β-arrestin interaction, trafficking, and signaling
Hemlata Dwivedi‐Agnihotri, Madhu Chaturvedi, Mithu Baidya, Tomasz Maciej Stępniewski, Shubhi Pandey, Jagannath Maharana, Ashish Srivastava, Natarin Caengprasath, Aylin C. Hanyaloglu, Jana Selent, Arun K. Shukla
Abstract
R, suitably positioned to cross-talk with a key residue in βarrs, has a decisive contribution in βarr recruitment, and its mutation results in strong G-protein bias. Molecular dynamics simulation provides mechanistic insights into the pivotal role of this key phosphorylation site in governing the stability of βarr interaction and regulating the interdomain rotation in βarrs. Our findings uncover important structural aspects to better understand the framework of GPCR-βarr interaction and biased signaling.
Topics & Concepts
PhosphorylationG protein-coupled receptorArrestinReceptorVasopressin receptorBiologyCell biologySignal transductionChemistryComputational biologyBiochemistryAntagonistReceptor Mechanisms and SignalingNeuroendocrine regulation and behaviorPhotoreceptor and optogenetics research