Molecular Determinants for Ligand Selectivity of the Cell-Free Synthesized Human Endothelin B Receptor.

摘要: Abstract Extracellular domains of G-protein-coupled receptors act as initial molecular selectivity filters for subtype specific ligands and drugs. Chimeras the human endothelin-B receptor containing structural units from extracellular endothelin-A were analyzed after their co-translational insertion into preformed nanodiscs. A short β-strand a linker region in second loop well parts N-terminal domain identified discrimination sites receptor-selective agonists IRL1620, sarafotoxin 6c, 4Ala-ET-1 ET-3, but not non-selective agonist ET-1 recognized by both endothelin receptors. proposed disulfide bridge tethering with third was essential recognition binding, increased thermostability. We further demonstrate an experimental approach cell-free synthesized engineered to analyze differential peptide ligand topologies two The study is based on engineering defined membranes may become interesting also other targets alternative platform reveal details binding mechanisms.