6zfd
From Proteopedia
14-3-3 zeta bound to the phosphorylated 18E6 C-terminus
Structural highlights
Function[1433Z_HUMAN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.[1] [2] [3] [4] [5] Publication Abstract from PubMedThe 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 KD 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. Hierarchized phosphotarget binding by the seven human 14-3-3 isoforms.,Gogl G, Tugaeva KV, Eberling P, Kostmann C, Trave G, Sluchanko NN Nat Commun. 2021 Mar 15;12(1):1677. doi: 10.1038/s41467-021-21908-8. PMID:33723253[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Gogl, G | Sluchanko, N N | Trave, G | Tugaeva, K V | 14-3-3 | E6 oncoprotein | Hpv | Protein binding
