Why Does Af 2 Allow Binding To Bind The Coactivators

Recognition of the coactivator: Nuclear receptors contains one ligand dependent transcriptional activation domain AF-2. Upon the agonist binding, AF-2 take an active conformation that allow it to bind the coactivators. AF-2 consists of the hydrophobic residues of helices 3, 4, 5 and 12. So, when the agonist is binding, helix 12 would take a conformation that allow it to complete the hydrophobic surface of AF-2 allow binding to LXXLL motifs of the coactivator [3]. The nuclear receptors are different in which motif they are binding to. For instance, GR and PR prefer binding to the third LXXLL motif. While, others like ERα and ERβ favor binding to the second motif LXXLL [1, 7]. The crystallization of the third motif LLRYLL of TIF-2 with