8HSV

The structure of rat beta-arrestin1 in complex with a rat Mdm2 peptide

8HSV の概要

• エントリーDOI: 10.2210/pdb8hsv/pdb
• 分子名称: Beta-arrestin-1, peptide from E3 ubiquitin-protein ligase Mdm2, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: arrestin, signaling protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 97307.65

構造登録者

Yun, Y.,Yoon, H.J.,Choi, Y.,Lee, H.H. (登録日: 2022-12-20, 公開日: 2023-07-19, 最終更新日: 2024-05-29)

主引用文献

Yun, Y.,Yoon, H.J.,Jeong, Y.,Choi, Y.,Jang, S.,Chung, K.Y.,Lee, H.H.
GPCR targeting of E3 ubiquitin ligase MDM2 by inactive beta-arrestin.
Proc.Natl.Acad.Sci.USA, 120:e2301934120-e2301934120, 2023

PubMed 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 peptide. The acidic residues of Mdm2 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 binding site of Mdm2 and GPCR C-tails on β-arrestin1 suggests that the binding of GPCR C-tails might trigger the release of Mdm2. Moreover, hydrogen/deuterium exchange experiments further show that Mdm2 binding to β-arrestin1 induces the interdomain interface to be more dynamic and uncouples the IP-induced oligomer of β-arrestin1. These results show how the E3 ligase, Mdm2, interacts with β-arrestins to promote the internalization of GPCRs.

PubMed: 37399373
DOI: 10.1073/pnas.2301934120

実験手法

X-RAY DIFFRACTION (3 Å)