The ligand binding domain (LBD) of apo-nuclear receptors (NRs) in solution is thought to be a very dynamic structure with many possible conformations. Upon ligand binding, the structure is stabilized to a more rigid conformation. The Dynamic Stabilization assay is a LBD re-assembly assay that takes advantage of the high specificity of the intramolecular interactions that comprise the ligand bound LBD. Here, we demonstrate Dynamic Stabilization for the NRs PPAR and NGFIB, and identify residues important for stabilization of the intramolecular interactions induced by PPAR ligands. Site directed mutatgenesis studies identified residues in helix 1 and helix 8 required for LBD re-assembly. Further, disrupting the helix 1/helix 8 interaction in the context of the holo-LBD alters the response of the receptor in a compound specific manner, suggesting that residues far from the ligand binding pocket can influence the stability of the ligand bound receptor. Thus, these results support and extend models of the apo-LBD of PPAR as a dynamic structure.