7A6Y

Structure of 14-3-3 gamma in complex with DAPK2 peptide stabilized by FC-A

7A6Y の概要

• エントリーDOI: 10.2210/pdb7a6y/pdb
• 分子名称: 14-3-3 protein gamma, DAPK2 C-terminal peptide, FUSICOCCIN, ... (4 entities in total)
• 機能のキーワード: 14-3-3 protein, dapk2, kinase, complex, phosphorylation, fusicoccin, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 114568.63

構造登録者

Horvath, M.,Obsilova, V.,Obsil, T. (登録日: 2020-08-27, 公開日: 2021-08-25, 最終更新日: 2024-11-06)

主引用文献

Horvath, M.,Petrvalska, O.,Herman, P.,Obsilova, V.,Obsil, T.
14-3-3 proteins inactivate DAPK2 by promoting its dimerization and protecting key regulatory phosphosites.
Commun Biol, 4:986-986, 2021

PubMed Abstract: Death-associated protein kinase 2 (DAPK2) is a CaM-regulated Ser/Thr protein kinase, involved in apoptosis, autophagy, granulocyte differentiation and motility regulation, whose activity is controlled by autoinhibition, autophosphorylation, dimerization and interaction with scaffolding proteins 14-3-3. However, the structural basis of 14-3-3-mediated DAPK2 regulation remains unclear. Here, we structurally and biochemically characterize the full-length human DAPK2:14-3-3 complex by combining several biophysical techniques. The results from our X-ray crystallographic analysis revealed that Thr369 phosphorylation at the DAPK2 C terminus creates a high-affinity canonical mode III 14-3-3-binding motif, further enhanced by the diterpene glycoside Fusicoccin A. Moreover, concentration-dependent DAPK2 dimerization is disrupted by Ca/CaM binding and stabilized by 14-3-3 binding in solution, thereby protecting the DAPK2 inhibitory autophosphorylation site Ser318 against dephosphorylation and preventing Ca/CaM binding. Overall, our findings provide mechanistic insights into 14-3-3-mediated DAPK2 inhibition and highlight the potential of the DAPK2:14-3-3 complex as a target for anti-inflammatory therapies.

PubMed: 34413451
DOI: 10.1038/s42003-021-02518-y

実験手法

X-RAY DIFFRACTION (2.5 Å)