GPCR targeting of E3 ubiquitin ligase MDM2 by inactive β-arrestin.

ABSTRACT: E3 ubiquitin ligase Mdm2 facilitates β-arrestin ubiquitination, leading to the internalization of G protein-coupled receptors (GPCRs). In this process, β-arrestins bind to Mdm2 and recruit it to the receptor; however, the molecular architecture of the β-arrestin-Mdm2 complex has not been elucidated yet. Here, we identified the β-arrestin-binding region (ABR) on Mdm2 and solved the crystal structure of β-arrestin1 in complex with Mdm2_ABR peptide. The acidic residues of Mdm2_ABR bind to the positively charged concave side of the β-arrestin1 N-domain. The C-tail of β-arrestin1 is still bound to the N-domain, indicating that Mdm2 binds to the inactive state of β-arrestin1, whereas the phosphorylated C-terminal tail of GPCRs binds to activate β-arrestins. The overlapped bin

SUBMITTER: Yun Y 

PROVIDER: S-EPMC10334748 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature