The 2.6 Å Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist
By Veli-Pekka Jaakola, Mark T. Griffith, M. Hanson, Vadim Cherezov, E. Chien, J. R. Lane, Adriaan P. IJzerman, Raymond C. Stevens. 2008
1,753 citations recorded by the source corpus.
The adenosine class of heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) mediates the important role of extracellular adenosine in many physiological processes and is antagonized by caffeine. We have determined the crystal structure of the human A2A adenosine receptor, in complex with a high-affinity subtype-selective antagonist, ZM241385, to 2.6 angstrom resolution. Four disulfide bridges in the extracellular domain, combined with a subtle repacking of the transmembrane helices relative to the adrenergic and rhodopsin receptor structures, define a pocket distinct from that of other structurally determined GPCRs. The arrangement allows for the binding of the antagonist in an extended conformation, perpendicular to the membrane plane. The binding site highlights an integral role for the extracellular loops, together with the helical core, in ligand recognition by this class of GPCRs and suggests a role for ZM241385 in restricting the movement of a tryptophan residue important in the activation mechanism of the class A receptors.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Physiology
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cellular and Molecular Neuroscience
- David E. Gloriam
- Brian K. Kobilka
- Raymond C. Stevens
- Vadim Cherezov
- Vsevolod Katritch
- Yang Zhang
- Jens Meiler
- Vignir Ísberg
In Molecular Biology
- Yang Zhang
- Jianyi Yang
- Jens Meiler
- Jian Zhang
- Brian K. Kobilka
- Vsevolod Katritch
- David E. Gloriam
- Gaetano T. Montelione
In Physiology
Citations in the corpus
- GOMoDo: A GPCRs Online Modeling and Docking Webserver (2013, methodology): “hA 2AR in complex with ZMA, whose crystal structure is available as PDB code 3EML [49] (UniProt ID: P29274).”
- Computing Highly Correlated Positions Using Mutual Information and Graph Theory for G Protein-Coupled Receptors (2009, background): “The recent publication of the crystal structure of the Adenosine A2A receptor also supports the presence of a common binding cavity [16].”
- Modern homology modeling of G-protein coupled receptors: which structural template to use? (2009, background): “In summary, there are currently 22 crystal structures of inverse agonist-bound class A GPCRs described in the literature 3 - 20 .”