7OPM

Phosphorylated ERK2 in complex with ORF45

7OPM の概要

• エントリーDOI: 10.2210/pdb7opm/pdb
• 分子名称: Mitogen-activated protein kinase 1, synthetic ERK2 inhibitor peptide, Protein ORF45, ... (6 entities in total)
• 機能のキーワード: mapk, erk2, phosphorylated erk2, orf45, kaposi's sarcoma-associated herpesvirus, fxfp-motif, viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 46365.17

構造登録者

Sok, P.,Remenyi, A.,Alexa, A.,Poti, A. (登録日: 2021-06-01, 公開日: 2022-02-02, 最終更新日: 2024-01-31)

主引用文献

Alexa, A.,Sok, P.,Gross, F.,Albert, K.,Kobori, E.,Poti, A.L.,Gogl, G.,Bento, I.,Kuang, E.,Taylor, S.S.,Zhu, F.,Ciliberto, A.,Remenyi, A.
A non-catalytic herpesviral protein reconfigures ERK-RSK signaling by targeting kinase docking systems in the host.
Nat Commun, 13:472-472, 2022

PubMed Abstract: The Kaposi's sarcoma associated herpesvirus protein ORF45 binds the extracellular signal-regulated kinase (ERK) and the p90 Ribosomal S6 kinase (RSK). ORF45 was shown to be a kinase activator in cells but a kinase inhibitor in vitro, and its effects on the ERK-RSK complex are unknown. Here, we demonstrate that ORF45 binds ERK and RSK using optimized linear binding motifs. The crystal structure of the ORF45-ERK2 complex shows how kinase docking motifs recognize the activated form of ERK. The crystal structure of the ORF45-RSK2 complex reveals an AGC kinase docking system, for which we provide evidence that it is functional in the host. We find that ORF45 manipulates ERK-RSK signaling by favoring the formation of a complex, in which activated kinases are better protected from phosphatases and docking motif-independent RSK substrate phosphorylation is selectively up-regulated. As such, our data suggest that ORF45 interferes with the natural design of kinase docking systems in the host.

PubMed: 35078976
DOI: 10.1038/s41467-022-28109-x

実験手法

X-RAY DIFFRACTION (2.45 Å)