Epitopes described in "Crystal structure of the human beta2 adrenergic G-protein-coupled receptor."

Article Authors:Søren G F Rasmussen; Hee-Jung Choi; Daniel M Rosenbaum; Tong Sun Kobilka; Foon Sun Thian; Patricia C Edwards; Manfred Burghammer; Venkata R P Ratnala; Ruslan Sanishvili; Robert F Fischetti; Gebhard F X Schertler; William I Weis; Brian K Kobilka
Article Title:Crystal structure of the human beta2 adrenergic G-protein-coupled receptor.
Reference Detail
Reference ID:1019683
Abstract:Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in detergent solutions. Here we report a structure of the human beta2 adrenoceptor (beta2AR), which was crystallized in a lipid environment when bound to an inverse agonist and in complex with a Fab that binds to the third intracellular loop. Diffraction data were obtained by high-brilliance microcrystallography and the structure determined at 3.4 A/3.7 A resolution. The cytoplasmic ends of the beta2AR transmembrane segments and the connecting loops are well resolved, whereas the extracellular regions of the beta2AR are not seen. The beta2AR structure differs from rhodopsin in having weaker interactions between the cytoplasmic ends of transmembrane (TM)3 and TM6, involving the conserved E/DRY sequences. These differences may be responsible for the relatively high basal activity and structural instability of the beta2AR, and contribute to the challenges in obtaining diffraction-quality crystals of non-rhodopsin GPCRs.
Reference Type:Literature
PubMed ID:17952055
Journal Volume:450
Article Pages:383-7
Journal ISSN:1476-4687
Article Chemical List:Adrenergic beta-2 Receptor Antagonists;Immunoglobulin Fab Fragments;Lipids;Receptors, Adrenergic, beta-2;Rhodopsin;Leucine
Article MeSH List:Adrenergic beta-2 Receptor Antagonists; Animals; Cell Line; Crystallization; Crystallography, X-Ray; Drug Inverse Agonism; Humans; Immunoglobulin Fab Fragments(chemistry; metabolism); Leucine(metabolism); Lipids(chemistry); Models, Molecular; Protein Conformation; Receptors, Adrenergic, beta-2(chemistry; metabolism); Rhodopsin(chemistry; metabolism); Spodoptera
Curation Last Updated:2014-10-03 22:06:12