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Structure of an agonist-bound human A2A adenosine receptor.


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.

SUBMITTER: Xu F 

PROVIDER: S-EPMC3086811 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Structure of an agonist-bound human A2A adenosine receptor.

Xu Fei F   Wu Huixian H   Katritch Vsevolod V   Han Gye Won GW   Jacobson Kenneth A KA   Gao Zhan-Guo ZG   Cherezov Vadim V   Stevens Raymond C RC  

Science (New York, N.Y.) 20110310 6027


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 t  ...[more]

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