Fig. 5.

Proposed model for the modulation of GR quaternary structure. Upon ligand binding, GR forms dimers through LBD–LBD and DBD–DBD interactions. DNA binding triggers an allosteric conformational change in the D-loop within the DBD. Also, the intrinsically disordered NTD may adopt a more defined structure upon DNA binding (6). By as yet unknown mechanisms, the conformational change in the DBD affects the LBD, and the receptor now undergoes a dimer-to-tetramer transition. Both head-to-head (1) and head-to-tail (2) configurations are equally plausible.