This research established a 3-state model of Gαs conformational landscape and quantitatively investigated the conformational transitions and dynamics of Gαs proteins in response to different ligand-bound receptors, enabling a novel GPCR model that integrates quantitative G protein conformational dynamics at the atomic level to explain GPCR pharmacological efficacy.
G-protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins involved in cellular signaling. Although X-ray crystallography and cryo-Electron Microscopy (cryo-EM) have provided valuable structural insights into GPCRs, these experimental techniques primarily capture static conformations and can...
Keya Joshi, V. Adediwura, Ying-Long Miao· Frontiers in Chemical Biolog...· 0 citations
G protein-coupled receptors (GPCRs) often engage multiple intracellular transducers, yet the structural basis by which endogenous ligands influence G protein selectivity remains poorly understood. GPR119 is a lipid-activated receptor expressed in pancreatic β-cells and enteroendocrine L-cells, where it regulates glucos...
Donggyun Kim, Mohsen Ranjbar, Aleksey Raskovalov et al.· bioRxiv· 0 citations
It is suggested that Gα protein selectivity is an allosterically encoded property of GPCRs and provide a conceptual framework for designing ligands and receptors with tailored Gα protein-biased signaling.
Tegvir S. Boora, Han-Yu Chen, Aaron Cho et al.· bioRxiv· 0 citations
G protein-coupled receptors (GPCRs) are membrane proteins that act as signal transducers across cell membranes. Class B1 GPCRs, a subset of 15 receptors activated by peptide hormones, are involved in important physiological processes and diseases, making them a popular target for drug development. GPCRs are dynamic pro...
Theodore J. Nettleton, P. M. Sexton, D. Wootten et al.· Biochemical Society Transact...· 0 citations
G protein-coupled receptors (GPCRs) represent the largest membrane protein family in the human body and the major targets of FDA-approved medications. Unlike some other physiological proteins, GPCRs are highly plastic and often exist as collections of conformational ensembles in the environment to exert their function....
This study established a native mass spectrometry platform to probe ligand-induced conformational heterogeneity at the GPCR intracellular interface and demonstrated the utility of nanobody-based nMS for evaluating the structural heterogeneity and dynamic landscapes of GPCRs.
