Scribble co-operatively binds multiple α_1D-adrenergic receptor C-terminal PDZ ligands.

ABSTRACT: Many G protein-coupled receptors (GPCRs) are organized as dynamic macromolecular complexes in human cells. Unraveling the structural determinants of unique GPCR complexes may identify unique protein:protein interfaces to be exploited for drug development. We previously reported α_1D-adrenergic receptors (α_1D-ARs) - key regulators of cardiovascular and central nervous system function - form homodimeric, modular PDZ protein complexes with cell-type specificity. Towards mapping α_1D-AR complex architecture, biolayer interferometry (BLI) revealed the α_1D-AR C-terminal PDZ ligand selectively binds the PDZ protein scribble (SCRIB) with >8x higher affinity than known interactors syntrophin, CASK and DLG1. Complementary in situ and in vitro assays revealed

SUBMITTER: Janezic EM 

PROVIDER: S-EPMC6773690 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature