Structural insights into the catalytic cycle of G protein-coupled receptor kinase 5 and a possible regulatory site for potassium ion.

ABSTRACT: G protein-coupled receptor (GPCR) kinases (GRKs) instigateGPCR desensitization, but despite many available structures, a molecular understanding of their function and catalytic cycle remains incomplete. We present six GRK5 crystal structures that capture both open and closed states of its kinase domain as well as complexes with the ligands sangivamycin (Sgv), an adenosine analog, and ATP. The Sgv-bound structure is distinct from the previously reported GRK5·Sgv structure and features an ordered N-terminal helix that docks to the kinase hinge, mimicking its interactions in GPCR or Ca²⁺·calmodulin-bound GRK complexes. GRK5 undergoes a dramatic conformational change in the crystals to a ligand-free, open state with a disordered N terminus when K⁺ is omitted from the harv

SUBMITTER: Chen Y 

PROVIDER: S-EPMC12268638 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature