Investigating the General Conformational Dynamics of G Protein-coupled Receptor Kinases (Grks) and Their Subfamilies

Abstract

G protein-coupled receptor kinases (GRKs) are essential regulators of signaling pathways mediated by G protein-coupled receptors (GPCRs). Recent research suggests that GRK-mediated phosphorylation patterns dictate functional selectivity, leading to biased cellular responses. However, a comprehensive understanding of the structural mechanisms at the single-residue level remains elusive. This study aims to employ computational methods to quantify the general conformational dynamics of GRKs, with a particular focus on quantifying their transitions between the open and close states. To facilitate a precise structural comparison, we assigned common labels to topologically identical positions across GRK structures retrieved from the Protein Data Bank (PDB). Our analysis showed both general and subfamily-specific dynamic movements associated with the open-close state transition. Elucidating these structural dynamics has the potential to provide significant insights into the functional diversity and regulatory mechanisms of GRK-mediated signaling.