8GP3

Structure of beta-arrestin1 in complex with a phosphopeptide corresponding to the human C-X-C chemokine receptor type 4, CXCR4

8GP3 の概要

• エントリーDOI: 10.2210/pdb8gp3/pdb
• EMDBエントリー: 34188
• 分子名称: Beta-arrestin-1, C-X-C chemokine receptor type 4, Fab30 Heavy Chain, ... (4 entities in total)
• 機能のキーワード: gpcr, 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: 8
• 化学式量合計: 196832.91

構造登録者

Maharana, J.,Sarma, P.,Yadav, M.K.,Banerjee, R.,Shukla, A.K. (登録日: 2022-08-25, 公開日: 2023-05-17, 最終更新日: 2024-11-13)

主引用文献

Maharana, J.,Sarma, P.,Yadav, M.K.,Saha, S.,Singh, V.,Saha, S.,Chami, M.,Banerjee, R.,Shukla, A.K.
Structural snapshots uncover a key phosphorylation motif in GPCRs driving beta-arrestin activation.
Mol.Cell, 83:2091-2107.e7, 2023

PubMed Abstract: Agonist-induced GPCR phosphorylation is a key determinant for the binding and activation of β-arrestins (βarrs). However, it is not entirely clear how different GPCRs harboring divergent phosphorylation patterns impart converging active conformation on βarrs leading to broadly conserved functional responses such as desensitization, endocytosis, and signaling. Here, we present multiple cryo-EM structures of activated βarrs in complex with distinct phosphorylation patterns derived from the carboxyl terminus of different GPCRs. These structures help identify a P-X-P-P type phosphorylation motif in GPCRs that interacts with a spatially organized K-K-R-R-K-K sequence in the N-domain of βarrs. Sequence analysis of the human GPCRome reveals the presence of this phosphorylation pattern in a large number of receptors, and its contribution in βarr activation is demonstrated by targeted mutagenesis experiments combined with an intrabody-based conformational sensor. Taken together, our findings provide important structural insights into the ability of distinct GPCRs to activate βarrs through a significantly conserved mechanism.

PubMed: 37209686
DOI: 10.1016/j.molcel.2023.04.025

実験手法

ELECTRON MICROSCOPY (4.8 Å)