2VT4

TURKEY BETA1 ADRENERGIC RECEPTOR WITH STABILISING MUTATIONS AND BOUND CYANOPINDOLOL

Summary for 2VT4

• Entry DOI: 10.2210/pdb2vt4/pdb
• Related: 1DEP 2R4R 2R4S 2RH1
• Descriptor: BETA1 ADRENERGIC RECEPTOR, Cyanopindolol, SODIUM ION, ... (6 entities in total)
• Functional Keywords: gpcr, membrane, receptor, palmitate, transducer, antagonist bound form, integral membrane protein, g-protein coupled receptor, g protein coupled receptor, thermostabilising point mutations, phosphoprotein, seven-helix receptor, lipoprotein, 7tm receptor, glycoprotein, transmembrane
• Biological source: MELEAGRIS GALLOPAVO (COMMON TURKEY)
• Total number of polymer chains: 4
• Total formula weight: 148237.55

Authors

Warne, A.,Serrano-Vega, M.J.,Baker, J.G.,Moukhametzianov, R.,Edwards, P.C.,Henderson, R.,Leslie, A.G.W.,Tate, C.G.,Schertler, G.F.X. (deposition date: 2008-05-09, release date: 2008-06-24, Last modification date: 2025-07-16)

Primary citation

Warne, A.,Serrano-Vega, M.J.,Baker, J.G.,Moukhametzianov, R.,Edwards, P.C.,Henderson, R.,Leslie, A.G.W.,Tate, C.G.,Schertler, G.F.X.
Structure of a Beta1-Adrenergic G-Protein-Coupled Receptor.
Nature, 454:486-, 2008

PubMed Abstract: G-protein-coupled receptors have a major role in transmembrane signalling in most eukaryotes and many are important drug targets. Here we report the 2.7 A resolution crystal structure of a beta(1)-adrenergic receptor in complex with the high-affinity antagonist cyanopindolol. The modified turkey (Meleagris gallopavo) receptor was selected to be in its antagonist conformation and its thermostability improved by earlier limited mutagenesis. The ligand-binding pocket comprises 15 side chains from amino acid residues in 4 transmembrane alpha-helices and extracellular loop 2. This loop defines the entrance of the ligand-binding pocket and is stabilized by two disulphide bonds and a sodium ion. Binding of cyanopindolol to the beta(1)-adrenergic receptor and binding of carazolol to the beta(2)-adrenergic receptor involve similar interactions. A short well-defined helix in cytoplasmic loop 2, not observed in either rhodopsin or the beta(2)-adrenergic receptor, directly interacts by means of a tyrosine with the highly conserved DRY motif at the end of helix 3 that is essential for receptor activation.

PubMed: 18594507
DOI: 10.1038/NATURE07101

Experimental method

X-RAY DIFFRACTION (2.7 Å)