Structure-Function Based Molecular Relationships in Ewing’s Sarcoma

Figure 3

Schematic model of the transcription complex (transactivation by the EAD), including some of the interacting partners of EWS, based on the EFPs fusion proteins. The EAD is bound to the promoter via the DNA-binding motif (DBM) in the DNA-binding domain (DBD) of the EFP (bZIP for the ATF1 as EFP), and Core Pol II binds DNA via the TBP TATA box of the transcription factor TFIID. The N-terminus of EAD directly contacts Rpb5 and Rpb7 via the N-terminus, while the intact EWS does not. The heterodimer Rpb4/7 binds to the EAD, thus connecting it to the Core RNA Pol II. The complex Rpb4/7 can stabilize the pre-initiation complexes by converting the conformation of RNA Pol II from open to closed. The Rpb7 is forming several direct contacts with Rpb1, Rpb2, and Rpb6 holding them together in a preferred conformation. The conformation of Pol II changes during different stages. The Core Pol II may adopt an open configuration, allowing the dsDNA to enter the active-site groove. The Rpb4/7 associates with Core Pol II through the N-terminal ribonucleoprotein-like domain of Rpb7 and the partially ordered N-terminal region of Rpb4. Some additional components, CBP, PKC, CaM, and ZFM1, interacting with the EAD, and RHA, interacting with EFP, are shown. DBD-DNA-binding domain. DBM-DNA-binding motif; for EAD-ATF1 the DBM is bZIP.