Sandbox 121: Difference between revisions

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==='''Introduction'''===

The Beta-2 Adrenergic Receptor (~~B2AR~~) is a G-protein coupled receptor (GPCR) which, when stimulated by a catecholamine, causes the relaxation of various smooth muscles, and the production of glucose by glycogenolysis and gluconeogenesis. Pharmaceuticals acting through B2AR are important for treating asthma, chronic obstructive pulmonary disease (COPD), and premature labor. The structure of B2AR consists of 7-transmembrane domains, connected by three extracellular loops and three intracellular loops. At the base of the extracellular loops, buried within the transmembrane helices, there is a predominately hydrophobic binding pocket with several crucial polar residues that interact with ligands. Interestingly, certain polar interactions appear to play a role in the conversion of the receptor from an active to an inactive state. Recent crystallography of B2AR has revealed that the active state, relative to the inactive state, shows only minor changes in the binding pocket, whereas critical shifts occur at the cytoplasmic face. These conformational changes lead to a dissociation of the G-protein from the receptor, which then initiates a signaling cascade. The Hostos-Lincoln Academy SMART team (Students Modeling A Research Topic) modeled ligands in complex with B2AR using 3D printing technology. Supported by grants from the HHMI Precollege Program and the Camille and Henry Dreyfus Foundation.

The Beta-2 Adrenergic Receptor (B₂AR) is a G-protein coupled receptor (GPCR) which, when stimulated by a catecholamine, causes the relaxation of various smooth muscles, and the production of glucose by glycogenolysis and gluconeogenesis. Pharmaceuticals acting through B2AR are important for treating asthma, chronic obstructive pulmonary disease (COPD), and premature labor. The structure of B2AR consists of 7-transmembrane domains, connected by three extracellular loops and three intracellular loops. At the base of the extracellular loops, buried within the transmembrane helices, there is a predominately hydrophobic binding pocket with several crucial polar residues that interact with ligands. Interestingly, certain polar interactions appear to play a role in the conversion of the receptor from an active to an inactive state. Recent crystallography of B2AR has revealed that the active state, relative to the inactive state, shows only minor changes in the binding pocket, whereas critical shifts occur at the cytoplasmic face. These conformational changes lead to a dissociation of the G-protein from the receptor, which then initiates a signaling cascade. The Hostos-Lincoln Academy SMART team (Students Modeling A Research Topic) modeled ligands in complex with B2AR using 3D printing technology. Supported by grants from the HHMI Precollege Program and the Camille and Henry Dreyfus Foundation.

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Following binding of NE, to either alpha or beta receptors, conformational changes in the receptor lead to a disassociation of the G protein from the cytoplasmic face of the receptor which activates a second messenger, initiating a signaling cascade.

==='''Structure of Beta 2 Adrenergic Receptor'''===

B2AR is a single chain that crosses the lipid membrane 7 times from the extracellular to cytoplasmic surface. There are 3 extracellular loops and 3 intracellular loops.1

B2AR is a single chain that crosses the lipid membrane 7 times from the extracellular to cytoplasmic surface.

There are 3 extracellular loops and 3 intracellular loops.

The binding pocket is located to the center of the extracellular surface.

Sandbox 121: Difference between revisions

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@@ Line 10: / Line 10: @@
 ==='''Introduction'''===
-The Beta-2 Adrenergic Receptor (B2AR) is a G-protein coupled receptor (GPCR) which, when stimulated by a catecholamine, causes the relaxation of various smooth muscles, and the production of glucose by glycogenolysis and gluconeogenesis. Pharmaceuticals acting through B2AR are important for treating asthma, chronic obstructive pulmonary disease (COPD), and premature labor. The structure of B2AR consists of 7-transmembrane domains, connected by three extracellular loops and three intracellular loops. At the base of the extracellular loops, buried within the transmembrane helices, there is a predominately hydrophobic binding pocket with several crucial polar residues that interact with ligands. Interestingly, certain polar interactions appear to play a role in the conversion of the receptor from an active to an inactive state. Recent crystallography of B2AR has revealed that the active state, relative to the inactive state, shows only minor changes in the binding pocket, whereas critical shifts occur at the cytoplasmic face. These conformational changes lead to a dissociation of the G-protein from the receptor, which then initiates a signaling cascade. The Hostos-Lincoln Academy SMART team (Students Modeling A Research Topic) modeled ligands in complex with B2AR using 3D printing technology. Supported by grants from the HHMI Precollege Program and the Camille and Henry Dreyfus Foundation.
+The Beta-2 Adrenergic Receptor (B₂AR) is a G-protein coupled receptor (GPCR) which, when stimulated by a catecholamine, causes the relaxation of various smooth muscles, and the production of glucose by glycogenolysis and gluconeogenesis. Pharmaceuticals acting through B2AR are important for treating asthma, chronic obstructive pulmonary disease (COPD), and premature labor. The structure of B2AR consists of 7-transmembrane domains, connected by three extracellular loops and three intracellular loops. At the base of the extracellular loops, buried within the transmembrane helices, there is a predominately hydrophobic binding pocket with several crucial polar residues that interact with ligands. Interestingly, certain polar interactions appear to play a role in the conversion of the receptor from an active to an inactive state. Recent crystallography of B2AR has revealed that the active state, relative to the inactive state, shows only minor changes in the binding pocket, whereas critical shifts occur at the cytoplasmic face. These conformational changes lead to a dissociation of the G-protein from the receptor, which then initiates a signaling cascade. The Hostos-Lincoln Academy SMART team (Students Modeling A Research Topic) modeled ligands in complex with B2AR using 3D printing technology. Supported by grants from the HHMI Precollege Program and the Camille and Henry Dreyfus Foundation.
@@ Line 23: / Line 23: @@
 Following binding of NE, to either alpha or beta receptors,  conformational changes in the receptor lead to a disassociation of the G protein from the cytoplasmic face of the receptor which activates a second messenger, initiating a signaling cascade.
+<applet load='3P0G' size='500' frame='true' align='right' scene='Sandbox_121/B2ar_struc/1' caption='B₂AR Active'/>
 ==='''Structure of Beta 2 Adrenergic Receptor'''===
-B2AR is a single chain that crosses the lipid membrane 7 times from the extracellular to cytoplasmic surface. There are 3 extracellular loops and 3 intracellular loops.1
+B2AR is a single chain that crosses the lipid membrane 7 times from the extracellular to cytoplasmic surface.
+There are 3 extracellular loops and 3 intracellular loops.
 The binding pocket is located to the center of the extracellular surface.