Peptide recognition, signaling and modulation of class B G protein-coupled receptors

Class B G protein-coupled receptors (GPCRs) are important drug targets in many human diseases, including type 2 diabetes, obesity, cardiovascular disease and neurodegeneration. Peptide hormones bind to these receptors through interactions with both the extracellular domain and transmembrane domain. Despite remarkable advances in structural studies of GPCRs, structural characterization of the full-length class B receptors remains extremely challenging due to their conformational complexity. The recently solved structures of class B GPCRs reveal the structural basis of peptide ligand recognition and modulation mechanisms of small molecule allosteric modulators. Furthermore, these structures provide essential insights into molecular mechanisms of class B GPCR signal transduction and modulation.