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From Proteopedia
Crystal structure of the human beta2 adrenoceptor
OverviewSee the topic Beta-2 Adrenergic Receptor. Structural highlights
FunctionBeta-adrenergic receptors are G Protein-Coupled Receptors, i.e. their action of catecholamine-induced activation of adenylate cyclase is mediated through the action of G proteins. Beta-2-adrenergic receptors are widely distributed in the respiratory tract and are found on many types of cells there, such as smooth muscle cells, epithelial and endothelial cells, mast cells and more[1]. The natural ligands for adrenoceptors are epinephrine\norepinephrine (it may be worth noting that the beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine). When these ligands bind to adrenoceptors they activate them (they are their natural agonists), which in the case of the beta-2-adrenergic receptor translates to the sympathetic effect in the respiratory tract, namely, bronchodilation. This is the reason that beta-2-adrenergic receptors are the main target in Asthma treatment - drugs that function as beta-2 agonists help to activate these receptors in a similar way to epinephrine\norepinephrine and help patients to deal with acute or chronic asthma symptoms. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedStructural 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. Crystal structure of the human beta2 adrenergic G-protein-coupled receptor.,Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK Nature. 2007 Nov 15;450(7168):383-7. Epub 2007 Oct 21. PMID:17952055[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
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Categories: Human | Mus musculus | Burghammer, M | Choi, H J | Edwards, P C | Fischetti, R F | Kobilka, B K | Kobilka, T S | Rasmussen, S G.F | Ratnala, V R | Rosenbaum, D M | Sanishvili, R | Schertler, G F | Thian, F S | Weis, W I | G-protein coupled receptor | Glycoprotein | Lipoprotein | Palmitate | Phosphorylation | Receptor | Signaling protein | Transducer | Transmembrane helix
