Recently, the Xu lab at iHuman Institute published a review paper on the journal “Trends in Biochemical Sciences” (doi:10.1016/j.tibs.2014.12.005). This article titled “The importance of ligands for G protein-coupled receptor stability” systematically analyzed the past GPCR structure and ligand data and shed a new opinion on the important role of ligand in GPCR crystallography and pharmacology. This work was led by the ShanghaiTech graduate student Zhang Xianjun, who is also the first author of this paper.
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. In this article, the authors 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.
This work is supported by the research funding from the ShanghaiTech University and Shanghai Municipal Government.