Structures of the First Extracellular Domain of CRF Receptors

Corticotropin releasing factor (CRF) receptors belong to the secretin family of G proteincoupled receptors (GPCRs) and are responsible for initiating endocrine stress responses and mediating anxiety related behaviors upon activation via stressors. The main binding site for the CRF ligands is the first extracellular domain (ECD) of the receptors. Several structures of ligand-free and ligand-bound ECDs were recently determined either by nuclear magnetic resonance (NMR) spectroscopy or X-ray crystallography. They reveal how the ligands bind through both hydrophobic and hydrophilic interactions to the ECDs, which is highly dynamic in the absence of ligands. It is the purpose of this review to discuss these structures with a particular focus on ligand-receptor interaction.