Crystal structure of the RAR-γ ligand-binding domain bound to all-trans retinoic acid

Abstract
The 2.0-Å crystal structure of the ligand-binding domain (LBD) of the human retinoic acid receptor (RAR)-γ bound to all-trans retinoic acid reveals the ligand-binding interactions and suggests an electrostatic guidance mechanism. The overall fold is similar to that of the human RXR-α apo-LBD, except for the carboxy-terminal part which folds back towards the LBD core, contributing to the hydrophobic ligand pocket and 'sealing' its entry site. We propose a 'mouse trap' mechanism whereby a ligand-induced conformational transition repositions the amphi-pathic α-helix of the AF-2 activating domain and forms a transcriptionally active receptor.