PDBsum entry 2vt4

Receptor

PDB id: 2vt4

Contents

Protein chains

274 a.a.

Ligands

P32 ×4

SOG ×12

D10 ×2

Metals

_NA ×4

Waters ×31

References listed in PDB file

Key reference

• Title: Structure of a beta1-Adrenergic g-Protein-Coupled receptor.
• Authors: T.Warne, M.J.Serrano-Vega, J.G.Baker, R.Moukhametzianov, P.C.Edwards, R.Henderson, A.G.Leslie, C.G.Tate, G.F.Schertler.
• Ref.: Nature, 2008, 454, 486-491.
• PubMed id: 18594507

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.

Secondary reference #1

• Title: Conformational thermostabilization of the beta1-Adrenergic receptor in a detergent-Resistant form.
• Authors: M.J.Serrano-Vega, F.Magnani, Y.Shibata, C.G.Tate.
• Ref.: Proc Natl Acad Sci U S A, 2008, 105, 877-882.
• PubMed id: 18192400