X-ray crystallography studies illustrated that the ligand-bound ESR1 interacts with LXXLL motif-containing NCOA3 (SRC3) through the ligand-binding domain (LBD) at the C-terminus of ESR1, which also has a ligand-dependent transactivation function (known as AF-2) (Brzozowski et al. 1997). Cryoelectron microscopy (cryo-EM) determined the quaternary structure of an active complex of DNA-bound ESR1, steroid receptor coactivator 3 (SRC3 or NCOA3), and a secondary coactivator (p300/EP300). Structural models suggests the following assembly mechanism for the complex: each of the two ligand-bound ESR1 monomers independently recruits one NCOA3 protein via the transactivation domain of ESR1;the two NCOA3s in turn bind to different regions of one p300 protein through multiple contacts (Yi P et al. 2015).
Carlquist, M, Brzozowski, AM, Bonn, T, Dauter, Z, Gustafsson, JA, Greene, GL, Pike, AC, Engström, O, Ohman, L, Hubbard, RE
O'Malley, BW, Pintilie, GD, Foulds, CE, Yi, P, Ludtke, SJ, Lanz, RB, Feng, Q, Chiu, W, Schmid, MF, Wang, Z
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