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Structure of the beta2 adrenergic receptor in the full agonist bound stateStructure of the beta2 adrenergic receptor in the full agonist bound state
Structural highlights
Publication Abstract from PubMedG-protein-coupled receptors (GPCRs) are seven-transmembrane proteins mediating cellular signals in response to extracellular stimuli. Although three-dimensional structures showcase snapshots that can be sampled in the process and nuclear magnetic resonance detects conformational equilibria, the mechanism by which agonist-activated GPCRs interact with various effectors remains elusive. Here, we used paramagnetic nuclear magnetic resonance for leucine amide resonances to visualize the structure of beta2-adrenoreceptor in the full agonist-bound state, without thermostabilizing mutations abolishing its activity. The structure exhibited a unique orientation of the intracellular half of the transmembrane helix 6, forming a cluster of G-protein-interacting residues. Furthermore, analyses of efficacy-dependent chemical shifts of the residues near the pivotal PIF microswitch identified an equilibrium among three conformations, including one responsible for the varied signal level in each ligand-bound state. Together, these results provide a structural basis for the dynamic activation of GPCRs and shed light on GPCR-mediated signal transduction. Structural equilibrium underlying ligand-dependent activation of beta2-adrenoreceptor.,Imai S, Yokomizo T, Kofuku Y, Shiraishi Y, Ueda T, Shimada I Nat Chem Biol. 2020 Jan 20. pii: 10.1038/s41589-019-0457-5. doi:, 10.1038/s41589-019-0457-5. PMID:31959965[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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