title: The importance of ligands for G protein-coupled receptor stability.
abstract: Traditionally, G protein-coupled receptor (GPCR) activity has been characterized by ligand properties including affinity (Ki), potency (IC50/EC50), efficacy (Emax), and kinetics (Kon/Koff). These properties are related to ligand residence time, a general index of drug-target interaction in vivo. Recent GPCR structure-function breakthroughs have all required ligand stabilization of the receptor in some manner, highlighting the natural instability of these important cell surface receptors. This research has initiated a new era of discovery that highlights the importance of ligand-receptor interactions beyond the traditional mindset. We propose that receptor stability is related to receptor folding and residence in the cell membrane, affording a new dimension that should be considered when studying receptor function.
authors.affiliation: iHuman Institute, ShanghaiTech University, 2F Building 6, 99 Haike Road, Pudong New District, Shanghai, 201210, China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: iHuman Institute, ShanghaiTech University, 2F Building 6, 99 Haike Road, Pudong New District, Shanghai, 201210, China.
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Stevens
authors.affiliation: iHuman Institute, ShanghaiTech University, 2F Building 6, 99 Haike Road, Pudong New District, Shanghai, 201210, China. Electronic address: xufei@shanghaitech.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled
keywords: GPCR stabilization; ligand residence time; receptor residence time