6ZFD

14-3-3 zeta bound to the phosphorylated 18E6 C-terminus

6ZFD の概要

• エントリーDOI: 10.2210/pdb6zfd/pdb
• 分子名称: 14-3-3 protein zeta/delta,Protein E6, GLYCEROL (3 entities in total)
• 機能のキーワード: hpv, e6 oncoprotein, 14-3-3, protein binding
• 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: 55157.90

構造登録者

Gogl, G.,Tugaeva, K.V.,Sluchanko, N.N.,Trave, G. (登録日: 2020-06-17, 公開日: 2021-02-17, 最終更新日: 2024-10-23)

主引用文献

Gogl, G.,Tugaeva, K.V.,Eberling, P.,Kostmann, C.,Trave, G.,Sluchanko, N.N.
Hierarchized phosphotarget binding by the seven human 14-3-3 isoforms.
Nat Commun, 12:1677-1677, 2021

PubMed Abstract: The seven 14-3-3 isoforms are highly abundant human proteins encoded by similar yet distinct genes. 14-3-3 proteins recognize phosphorylated motifs within numerous human and viral proteins. Here, we analyze by X-ray crystallography, fluorescence polarization, mutagenesis and fusicoccin-mediated modulation the structural basis and druggability of 14-3-3 binding to four E6 oncoproteins of tumorigenic human papillomaviruses. 14-3-3 isoforms bind variant and mutated phospho-motifs of E6 and unrelated protein RSK1 with different affinities, albeit following an ordered affinity ranking with conserved relative K ratios. Remarkably, 14-3-3 isoforms obey the same hierarchy when binding to most of their established targets, as supported by literature and a recent human complexome map. This knowledge allows predicting proportions of 14-3-3 isoforms engaged with phosphoproteins in various tissues. Notwithstanding their individual functions, cellular concentrations of 14-3-3 may be collectively adjusted to buffer the strongest phosphorylation outbursts, explaining their expression variations in different tissues and tumors.

PubMed: 33723253
DOI: 10.1038/s41467-021-21908-8

実験手法

X-RAY DIFFRACTION (1.9 Å)