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Structure of an agonist-bound human A2A adenosine receptor.
- Source :
-
Science (New York, N.Y.) [Science] 2011 Apr 15; Vol. 332 (6027), pp. 322-7. Date of Electronic Publication: 2011 Mar 10. - Publication Year :
- 2011
-
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.
- Subjects :
- Adenosine chemistry
Adenosine metabolism
Adenosine A2 Receptor Agonists chemistry
Binding Sites
Crystallography, X-Ray
Humans
Hydrogen Bonding
Ligands
Models, Molecular
Opsins chemistry
Opsins metabolism
Protein Conformation
Protein Structure, Secondary
Rhodopsin chemistry
Rhodopsin metabolism
Triazines chemistry
Triazines metabolism
Triazoles chemistry
Triazoles metabolism
Adenosine analogs & derivatives
Adenosine A2 Receptor Agonists metabolism
Receptor, Adenosine A2A chemistry
Receptor, Adenosine A2A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 332
- Issue :
- 6027
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 21393508
- Full Text :
- https://doi.org/10.1126/science.1202793