Atomistic simulations shed new light on the activation mechanisms of RORγ and classify it as Type III nuclear hormone receptor regarding ligand-binding paths.

ABSTRACT: The molecular recognition of the RORγ nuclear hormone receptor (NHR) ligand-binding domain (LBD) has been extensively studied with numerous X-ray crystal structures. However, the picture afforded by these complexes is static and does not fully explain the functional behavior of the LBD. In particular, the apo structure of the LBD seems to be in a fully active state, with no obvious differences to the agonist-bound structure. Further, several atypical in vivo inverse agonists have surprisingly been found to co-crystallize with the LBD in agonist mode (with co-activator), leading to a disconnection between molecular recognition and functional activity. Moreover, the experimental structures give no clues on how RORγ LBD binders access the interior of the LBD. To address all these points, we p

SUBMITTER: Saen-Oon S 

PROVIDER: S-EPMC6872664 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature