The Intrinsic structural disorder (ISD) of native EWS and its fusion oncogenic proteins, including EWS/FliI, EWS/ATF1 and EWS/ZSG, was estimated by different Predictors. The ISD difference between the wild type and the oncogenic fusions found in the CTD is due to the fusion partner, usually a transcription factor (TF). A disordered region was found in the sequence (AA 132 - 156) of the NTD (EAD) of EWS, consisting of the longest region free of Y motifs. The IQ domain (AA 258 - 280), a Y-free region, flanked by two Y-boxes, is also disordered by all used Predictors. The EWS functional regions RGG1, RGG2 and RGG3 are predominantly disordered. A strong dependence was found between the structure of EWS protein and its oncogenic fusions, and their estimated ISD. The oncogenic function of the fusions is related to a decreased ISD in the CTD, due to the fused TF. The Predictors shown that the different isoforms have similar profiles, shifted with some amino acids, due to the translocations. On the bases of the prediction results, an analysis was made of the EWS sequence and its functional regions with increased ISD to make a relationship sequence-disorder-function that could be helpful in the design of antitumor agents against the corresponding malignances.
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