6KR8

Structure of the beta2 adrenergic receptor in the full agonist bound state

Summary for 6KR8

• Entry DOI: 10.2210/pdb6kr8/pdb
• NMR Information: BMRB: 36284
• Descriptor: beta 2 adrenergic receptor (1 entity in total)
• Functional Keywords: g-protein coupled receptor, b2ar, full agonist, membrane protein
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 38557.98

Authors

Imai, S.,Shimada, I. (deposition date: 2019-08-21, release date: 2020-01-29, Last modification date: 2020-04-08)

Primary citation

Imai, S.,Yokomizo, T.,Kofuku, Y.,Shiraishi, Y.,Ueda, T.,Shimada, I.
Structural equilibrium underlying ligand-dependent activation of beta2-adrenoreceptor.
Nat.Chem.Biol., 16:430-439, 2020

PubMed Abstract: G-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 β-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.

PubMed: 31959965
DOI: 10.1038/s41589-019-0457-5

Experimental method

SOLUTION NMR