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.
Keywords: GPCR, CRF receptors, first extracellular domain, structure, ligand binding, ECD.
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