6ZFD

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

Summary for 6ZFD

• Entry DOI: 10.2210/pdb6zfd/pdb
• Descriptor: 14-3-3 protein zeta/delta,Protein E6, GLYCEROL (3 entities in total)
• Functional Keywords: hpv, e6 oncoprotein, 14-3-3, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 55157.90

Authors

Gogl, G.,Tugaeva, K.V.,Sluchanko, N.N.,Trave, G. (deposition date: 2020-06-17, release date: 2021-02-17, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)