6zfd
From Proteopedia
14-3-3 zeta bound to the phosphorylated 18E6 C-terminus
Structural highlights
FunctionVE6_HPV18 Transcriptional transactivator. Binds double stranded DNA (By similarity). Has transforming activity. Inactivates, with E6-AP ubiquitin-protein ligase, the human p53/TP53 tumor suppressor protein by targeting it to degradation. Binds and targets human MUPP1/MPDZ protein to degradation. Those two functions presumably contribute to transforming activity. Interaction with human FBLN1 protein also seems to be linked to cell transformation.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
| ||||||||||||||||||||
