Structure of an Agonist-Bound Human A 2A Adenosine Receptor

2011/03/10 by Fei Xu, Huixian Wu, Vsevolod Katritch +5 · 1 citation
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Receptor Mechanisms and Signaling #Neuropeptides and Animal Physiology #Adenosine and Purinergic Signaling

paper · doi:10.1126/science.1202793

openalex publication_date 2011/03/10 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/01

Abstract

Activation of G protein-coupled receptors upon agonist binding is a critical step in the signaling cascade for this family of cell surface proteins. We report the crystal structure of the A(2A) adenosine receptor (A(2A)AR) bound to an agonist UK-432097 at 2.7 angstrom resolution. Relative to inactive, antagonist-bound A(2A)AR, the agonist-bound structure displays an outward tilt and rotation of the cytoplasmic half of helix VI, a movement of helix V, and an axial shift of helix III, resembling the changes associated with the active-state opsin structure. Additionally, a seesaw movement of helix VII and a shift of extracellular loop 3 are likely specific to A(2A)AR and its ligand. The results define the molecule UK-432097 as a "conformationally selective agonist" capable of receptor stabilization in a specific active-state configuration.

Citations

• Crystal structure of the human β2 adrenergic G-protein-coupled receptor
• Structure of a nanobody-stabilized active state of the β2 adrenoceptor
• GPCR Engineering Yields High-Resolution Structural Insights into β 2 -Adrenergic Receptor Function
• High-Resolution Crystal Structure of an Engineered Human β 2 -Adrenergic G Protein–Coupled Receptor
• The structural basis for agonist and partial agonist action on a β1-adrenergic receptor
• Structure and function of an irreversible agonist-β2 adrenoceptor complex

Cited by

• G protein-coupled receptor [wikipedia]