Adrenergic receptor

From Proteopedia

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Crystal Structure of β-2 Adrenergic Receptor, 2rh1

spinqualitylabelsall models β-2 Adrenergic Receptor (grey) complex with antibody heavy chain (red) and light chain (aqua) (PDB code 2r4r). Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 3D Structures of Adrenergic receptor 4 Nobel Prize Related to the Structures Function The adrenergic receptors are metabolic G protein-coupled receptors. They are the targets of catecholamines. The binding of an agonist to them causes a sympathetic response. The α-2 adrenergic receptor (A2AR) inhibits insulin or glucagons release. The β-1 adrenergic receptor (B1AR) increases cardiac output and secretion of rennin and ghrelin.[1] The β-2 adrenergic receptor (B2AR) triggers many relaxation reactions. See Beta-2 adrenergic receptor and Beta2 adrenergic receptor-Gs protein complex updated The β-3 adrenergic receptor (B3AR) is active in lipid metabolism.[2] See also G protein-coupled receptor Beta2 adrenergic receptor-Gs protein complex The Madison West High School 2008 SMART Team's Page on the β-2 adrenergic receptor UMass Chem 423 Student Projects 2011-1 Neurodevelopmental Disorders Transmembrane (cell surface) receptors. (morph was taken from Gallery of Morphs of the Yale Morph Server).   β2 adrenergic receptor binding a hormone analog and complexed to a heterotrimeric G protein (3sn6)   spinqualitylabelsall models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image An activated G protein-coupled receptor (human β-2 adrenergic receptor in blue ) in a complex with a heterotrimeric G protein (3 subunits:reddish to orange-brown) and hormone (gold) (3sn6), resolution 3.2Å. The boundaries of the membrane in which the GPCR sits are represented in light green. Relevance Alprenolol and Propranolol are B2AR antagonists used in treatment of angina pectoris. Timolol ia a B2AR antagonist used in treatment of glaucoma. Carvedilol is A2AR and B2AR antagonist used in treatment of high blood pressure. Salbutamol (Ventolin) and Salmeterol are B2AR agonists used for muscle relaxation in asthma attacks. 3D Structures of Adrenergic receptor Adrenergic receptor 3D structures This is the first structure of an activated GPCR in a complex with its G protein. Nobel Prize Related to the Structures Robert J. Lefkowitz and Brian K. Kobilka share the 2012 Nobel Prize in Chemistry for work on GPCRs that includes solving the first structures of a ligand-activated GPCR (2r4r, 2r4s, & 2rh1 in 2007)[3][4][5] and the first activated GPCR in complex with its G protein (3sn6 in 2011)[6][7][8][9]. A detailed description of the laureates' body of work on this class of receptors with images is here.

References

1. ↑ Huang J, Chen S, Zhang JJ, Huang XY. Crystal structure of oligomeric beta1-adrenergic G protein-coupled receptors in ligand-free basal state. Nat Struct Mol Biol. 2013 Apr;20(4):419-25. doi: 10.1038/nsmb.2504. Epub 2013 Feb, 24. PMID:23435379 doi:10.1038/nsmb.2504
2. ↑ Strosberg AD. Structure and function of the beta 3-adrenergic receptor. Annu Rev Pharmacol Toxicol. 1997;37:421-50. PMID:9131260 doi:10.1146/annurev.pharmtox.37.1.421
3. ↑ Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science. 2007 Nov 23;318(5854):1258-65. Epub 2007 Oct 25. PMID:17962520
4. ↑ Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK. GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science. 2007 Nov 23;318(5854):1266-73. Epub 2007 Oct 25. PMID:17962519
5. ↑ Ranganathan R. Biochemistry. Signaling across the cell membrane. Science. 2007 Nov 23;318(5854):1253-4. PMID:18033872 doi:10.1126/science.1151656
6. ↑ Schwartz TW, Sakmar TP. Structural biology: snapshot of a signalling complex. Nature. 2011 Sep 28;477(7366):540-1. doi: 10.1038/477540a. PMID:21956322 doi:10.1038/477540a
7. ↑ Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah ST, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK. Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature. 2011 Jul 19;477(7366):549-55. doi: 10.1038/nature10361. PMID:21772288 doi:10.1038/nature10361
8. ↑ Chung KY, Rasmussen SG, Liu T, Li S, DeVree BT, Chae PS, Calinski D, Kobilka BK, Woods VL Jr, Sunahara RK. Conformational changes in the G protein Gs induced by the beta2 adrenergic receptor. Nature. 2011 Sep 28;477(7366):611-5. doi: 10.1038/nature10488. PMID:21956331 doi:10.1038/nature10488
9. ↑ Schwartz TW, Sakmar TP. Structural biology: snapshot of a signalling complex. Nature. 2011 Sep 28;477(7366):540-1. doi: 10.1038/477540a. PMID:21956322 doi:10.1038/477540a

See Also

• G protein-coupled receptor
• Beta-2 Adrenergic Receptor topic page
• Nobel Prizes for 3D Molecular Structure
• Highest impact structures of all time
• G proteins
• Rhodopsin
• GTP-binding protein
• Pharmaceutical Drugs
• Membrane proteins
• Hormone
• Receptor
• Transmembrane (cell surface) receptors

External Resources

• Robert J. Lefkowitz and Brian K. Kobilka share the 2012 Nobel Prize in Chemistry for work on GPCRs that includes solving the first structures of a ligand-activated GPCR (2007) and the first activated GPCR in complex with its G protein (2011). A detailed description of the laureates' body of work on this class of receptors with images is here.
• The April 2008 RCSB PDB Molecule of the Month feature on Adrenergic Receptors by David S. Goodsell is 10.2210/rcsb_pdb/mom_2008_4.