4EIY

Crystal structure of the chimeric protein of A2aAR-BRIL in complex with ZM241385 at 1.8A resolution

Summary for 4EIY

• Entry DOI: 10.2210/pdb4eiy/pdb
• Related: 3eml
• Descriptor: Adenosine receptor A2a/Soluble cytochrome b562 chimera, 4-{2-[(7-amino-2-furan-2-yl[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino]ethyl}phenol, SODIUM ION, ... (9 entities in total)
• Functional Keywords: novel protein engineering, gpcr network, psi-biology, structural genomics, membrane protein, gpcr
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P29274
• Total number of polymer chains: 1
• Total formula weight: 58721.97

Authors

Liu, W.,Chun, E.,Thompson, A.A.,Chubukov, P.,Xu, F.,Katritch, V.,Han, G.W.,Heitman, L.H.,Ijzerman, A.P.,Cherezov, V.,Stevens, R.C.,GPCR Network (GPCR) (deposition date: 2012-04-06, release date: 2012-07-25, Last modification date: 2024-11-06)

Primary citation

Liu, W.,Chun, E.,Thompson, A.A.,Chubukov, P.,Xu, F.,Katritch, V.,Han, G.W.,Roth, C.B.,Heitman, L.H.,IJzerman, A.P.,Cherezov, V.,Stevens, R.C.
Structural basis for allosteric regulation of GPCRs by sodium ions.
Science, 337:232-236, 2012

PubMed Abstract: Pharmacological responses of G protein-coupled receptors (GPCRs) can be fine-tuned by allosteric modulators. Structural studies of such effects have been limited due to the medium resolution of GPCR structures. We reengineered the human A(2A) adenosine receptor by replacing its third intracellular loop with apocytochrome b(562)RIL and solved the structure at 1.8 angstrom resolution. The high-resolution structure allowed us to identify 57 ordered water molecules inside the receptor comprising three major clusters. The central cluster harbors a putative sodium ion bound to the highly conserved aspartate residue Asp(2.50). Additionally, two cholesterols stabilize the conformation of helix VI, and one of 23 ordered lipids intercalates inside the ligand-binding pocket. These high-resolution details shed light on the potential role of structured water molecules, sodium ions, and lipids/cholesterol in GPCR stabilization and function.

PubMed: 22798613
DOI: 10.1126/science.1219218

Experimental method

X-RAY DIFFRACTION (1.8 Å)