Description
Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:1.8
Classification:MEMBRANE PROTEIN
Release Date:2012-07-25
Deposition Date:2012-04-06
Revision Date:2012-08-01#2017-08-16
Molecular Weight:58721.96
Macromolecule Type:Protein
Residue Count:447
Atom Site Count:3586
DOI:10.2210/pdb4eiy/pdb
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.
Resolution:1.8
Classification:MEMBRANE PROTEIN
Release Date:2012-07-25
Deposition Date:2012-04-06
Revision Date:2012-08-01#2017-08-16
Molecular Weight:58721.96
Macromolecule Type:Protein
Residue Count:447
Atom Site Count:3586
DOI:10.2210/pdb4eiy/pdb
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.
| Date made available | 2012 |
|---|---|
| Publisher | RCSB-PDB |