title: Emerging structural insights into biased GPCR signaling.
abstract: The discovery of biased signaling at G protein-coupled receptors (GPCRs), the largest class of cell surface receptors and primary drug targets for numerous human diseases, has redefined the classical concepts of receptor pharmacology. It not only highlights the depth of signaling diversity within the GPCR system, but also offers possibilities for novel and more-effective therapeutics. Here, we highlight the recent biophysical and structural advances in our understanding of ligand-receptor interactions and conformational changes in the receptors, which provide novel mechanistic insights into biased GPCR signaling. We also underline key aspects of GPCR-biased signaling that remain to be investigated in greater detail to develop a complete molecular understanding of this process and overall GPCR signaling.
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India. Electronic address: arshukla@iitk.ac.in.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Shukla
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Singh
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India.
authors.forename: Eshan
authors.initials: E
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled
keywords: G protein-coupled receptors (GPCRs); biased agonism; biased signaling; β-arrestin; β2 adrenergic receptor’