Figure 2. Ligand-to-Ligand Allostery.

A. In nuclear receptor heterodimers, the conformational changes (blue arrow) induced within one receptor subunit upon binding its cognate ligand (green) are transmitted to the ligand-binding pocket of the second receptor (green). B. (a) The allosteric pathway from one ligand-binding pocket to the second includes the formation of both new interactions and the breaking of old interactions, as determined by the program CAMERRA (Q. R. Johnson, et al., 2015). (b) The result of these allosteric conformational changes are cooperative implying that the binding of ligand to one ligand-binding pocket can facilitate the binding of ligand to the second binding pocket in the nuclear receptor heterodimer. (c) Conversely, anticooperative binding occurs when the binding of ligand to one binding pocket diminishes the binding-affinity of the second binding pocket for ligand. Adapted with permission from (Clark, et al., 2016). Copyright (2016) American Chemical Society.