7p70

The PDZ-domain of SNTB1 complexed with the PDZ-binding motif of HPV35-E6

spinqualitylabelsall models 7p70, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7p70 is a 2 chain structure with sequence from Homo sapiens and Human papillomavirus 35. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: CA, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VE6_HPV35 This protein may be involved in the oncogenic potential of this virus (associated with cancer of the uterine cervix). Plays a major role in the induction and maintenance of cellular transformation. Acts mainly as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. E6 associates with host UBE3A/E6-AP ubiquitin-protein ligase, and inactivates tumor suppressors TP53 and TP73 by targeting them to the 26S proteasome for degradation. In turn, DNA damage and chromosomal instabilities increase and lead to cell proliferation and cancer development. The complex E6/E6AP targets several other substrates to degradation via the proteasome including host DLG1 or NFX1, a repressor of human telomerase reverse transcriptase (hTERT). The resulting increased expression of hTERT prevents the shortening of telomere length leading to cell immortalization. Other cellular targets including BAK1, Fas-associated death domain-containing protein (FADD) and procaspase 8, are degraded by E6/E6AP causing inhibition of apoptosis. E6 also inhibits immune response by interacting with host IRF3 and TYK2. These interactions prevent IRF3 transcriptional activities and inhibit TYK2-mediated JAK-STAT activation by interferon alpha resulting in inhibition of the interferon signaling pathway.[HAMAP-Rule:MF_04006] See Also Syntrophin

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