2ypr

Crystal structure of the DNA binding ETS domain of human protein FEV

spinqualitylabelsall models 2ypr, resolution 2.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ypr is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [FEV_HUMAN] Disease susceptibility may be associated with variations affecting the gene represented in this entry. A chromosomal aberration involving FEV is found in Ewing tumors. Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with a potential oncogenic activity. Function [FEV_HUMAN] Functions as a transcriptional regulator. According to PubMed:12761502, it functions as a transcriptional repressor. Functions in the differentiation and the maintenance of the central serotonergic neurons. May play a role in cell growth. Publication Abstract from PubMed Ets transcription factors, which share the conserved Ets DNA-binding domain, number nearly 30 members in humans and are particularly involved in developmental processes. Their deregulation following changes in expression, transcriptional activity, or by chromosomal translocation, plays a critical role in carcinogenesis. Ets DNA-binding, selectivity and regulation have been extensively studied, although questions still arise regarding binding specificity outside the core GGA recognition sequence, and the mode of action of Ets post-translational modifications. Here we report the crystal structures of ETV1, ETV4, ETV5 and FEV, alone and in complex with DNA. We identify previously unrecognized features of the protein-DNA interface. Interactions with the DNA backbone account for most of the binding affinity. We describe a highly coordinated network of water molecules acting in base selection upstream of the GGAA core, and the structural features that may account for discrimination against methylated cytidine residues. Unexpectedly, all proteins crystallized as disulfide-linked dimers, exhibiting a novel interface (distant to the DNA recognition helix). Homodimers of ETV1, ETV4 and ETV5 could be reduced to monomers, leading to a 40-200-fold increase in DNA binding affinity. Hence, we present the first indication of a redox-dependent regulatory mechanism which may control the activity of this subset of oncogenic Ets transcription factors. Structures of the Ets Domains of Transcription Factors ETV1, ETV4, ETV5 and FEV: Determinants of DNA Binding and Redox Regulation by Disulfide bond formation.,Cooper CD, Newman JA, Aitkenhead H, Allerston CK, Gileadi O J Biol Chem. 2015 Apr 12. pii: jbc.M115.646737. PMID:25866208 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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