6ZQS

Crystal structure of double-phosphorylated p38alpha with ATF2(83-102)

6ZQS の概要

• エントリーDOI: 10.2210/pdb6zqs/pdb
• 分子名称: Mitogen-activated protein kinase 14, Cyclic AMP-dependent transcription factor ATF-2, 2-[(2,4-difluorophenyl)amino]-7-{[(2R)-2,3-dihydroxypropyl]oxy}-10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-one, ... (4 entities in total)
• 機能のキーワード: transcription, mapk signaling pathways
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44374.17

構造登録者

Kirsch, K.,Sok, P.,Poti, A.L.,Remenyi, A. (登録日: 2020-07-10, 公開日: 2020-11-18, 最終更新日: 2024-11-06)

主引用文献

Kirsch, K.,Zeke, A.,Toke, O.,Sok, P.,Sethi, A.,Sebo, A.,Kumar, G.S.,Egri, P.,Poti, A.L.,Gooley, P.,Peti, W.,Bento, I.,Alexa, A.,Remenyi, A.
Co-regulation of the transcription controlling ATF2 phosphoswitch by JNK and p38.
Nat Commun, 11:5769-5769, 2020

PubMed Abstract: Transcription factor phosphorylation at specific sites often activates gene expression, but how environmental cues quantitatively control transcription is not well-understood. Activating protein 1 transcription factors are phosphorylated by mitogen-activated protein kinases (MAPK) in their transactivation domains (TAD) at so-called phosphoswitches, which are a hallmark in response to growth factors, cytokines or stress. We show that the ATF2 TAD is controlled by functionally distinct signaling pathways (JNK and p38) through structurally different MAPK binding sites. Moreover, JNK mediated phosphorylation at an evolutionarily more recent site diminishes p38 binding and made the phosphoswitch differently sensitive to JNK and p38 in vertebrates. Structures of MAPK-TAD complexes and mechanistic modeling of ATF2 TAD phosphorylation in cells suggest that kinase binding motifs and phosphorylation sites line up to maximize MAPK based co-regulation. This study shows how the activity of an ancient transcription controlling phosphoswitch became dependent on the relative flux of upstream signals.

PubMed: 33188182
DOI: 10.1038/s41467-020-19582-3

実験手法

X-RAY DIFFRACTION (1.95 Å)