6zfg

<table><tr><td colspan='2'>[[6zfg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_papillomavirus_type_18 Human papillomavirus type 18]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZFG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZFG FirstGlance]. <br>

== Function ==

[https://www.uniprot.org/uniprot/VE6_HPV18 VE6_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.[https://www.uniprot.org/uniprot/1433Z_HUMAN 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.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref>

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== Publication Abstract from PubMed ==

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 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<ref>PMID:33723253</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Homo sapiens]]

[[Category: Human papillomavirus type 18]]