Sandbox Reserved 1180: Difference between revisions

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===Structure===

The class B GPCRs, including GCGR, are different from other GPCRs in several ways. The first is that class B GPCRs contain a protrusion known as a 'stalk,' a three α-helical turn elongation of the N-terminus that protrudes past the extracellular (EC) membrane. Structural integrity of this domain in GCGR is <scene name='72/721552/~~Ligand_binding_interactions~~/1'>essential to ligand binding affinity</scene>. A135P mutations impact stalk stability by removing an important salt bridge between Glu133 - Lys136. A second difference between class B and other GPCRs is that the extracellular loop 1 (ECL1) is 3-4 times longer than comparable loops in class A GPCRs, and also affects ligand binding affinity.<ref name= "Siu 2013"/> Most notably, class B GPCRs contain a <scene name='72/727091/Corticotropin_glucagon_aligned/1'>prominent central splay</scene> which is solvent filled and accessible from the extracellular side. This central splay is notably absent <scene name='72/727091/B2-adrenergic_glucagon_aligned/9'>from other GPCRs</scene>, and represents a tantalizing target for agonists/antagonists.<ref name= "Hollenstein 2014"/>

The class B GPCRs, including GCGR, are different from other GPCRs in several ways. The first is that class B GPCRs contain a protrusion known as a 'stalk,' a three α-helical turn elongation of the N-terminus that protrudes past the extracellular (EC) membrane. Structural integrity of this domain in GCGR is <scene name='72/721552/The_right_one/3'>essential to ligand binding affinity.</scene> A135P mutations impact stalk stability by removing an important salt bridge between Glu133 - Lys136. A second difference between class B and other GPCRs is that the extracellular loop 1 (ECL1) is 3-4 times longer than comparable loops in class A GPCRs, and also affects ligand binding affinity.<ref name= "Siu 2013"/> Most notably, class B GPCRs contain a <scene name='72/727091/Corticotropin_glucagon_aligned/1'>prominent central splay</scene> which is solvent filled and accessible from the extracellular side. This central splay is notably absent <scene name='72/727091/B2-adrenergic_glucagon_aligned/9'>from other GPCRs</scene>, and represents a tantalizing target for agonists/antagonists.<ref name= "Hollenstein 2014"/>

Because of the difficulty in stabilizing and crystallizing Class B TMDs, very little is known about the conformational changes that transduce cell signals endogenously. GCGR is known to regulate additional signal pathways through the adoption of differing receptor conformations and to interact with receptor activity-modifying proteins (RAMPs) altering the signaling bias of the receptor.<ref name= "Xu 2009"/>

Sandbox Reserved 1180: Difference between revisions

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 ===Structure===
-The class B GPCRs, including GCGR, are different from other GPCRs in several ways.  The first is that class B GPCRs contain a protrusion known as a 'stalk,' a three α-helical turn elongation of the N-terminus that protrudes past the extracellular (EC) membrane.  Structural integrity of this domain in GCGR is <scene name='72/721552/Ligand_binding_interactions/1'>essential to ligand binding affinity</scene>.  A135P mutations impact stalk stability by removing an important salt bridge between Glu133 - Lys136.  A second difference between class B and other GPCRs is that the extracellular loop 1 (ECL1) is 3-4 times longer than comparable loops in class A GPCRs, and also affects ligand binding affinity.<ref name= "Siu 2013"/>  Most notably, class B GPCRs contain a <scene name='72/727091/Corticotropin_glucagon_aligned/1'>prominent central splay</scene> which is solvent filled and accessible from the extracellular side.  This central splay is notably absent <scene name='72/727091/B2-adrenergic_glucagon_aligned/9'>from other GPCRs</scene>, and represents a tantalizing target for agonists/antagonists.<ref name= "Hollenstein 2014"/>
+The class B GPCRs, including GCGR, are different from other GPCRs in several ways.  The first is that class B GPCRs contain a protrusion known as a 'stalk,' a three α-helical turn elongation of the N-terminus that protrudes past the extracellular (EC) membrane.  Structural integrity of this domain in GCGR is <scene name='72/721552/The_right_one/3'>essential to ligand binding affinity.</scene> A135P mutations impact stalk stability by removing an important salt bridge between Glu133 - Lys136.  A second difference between class B and other GPCRs is that the extracellular loop 1 (ECL1) is 3-4 times longer than comparable loops in class A GPCRs, and also affects ligand binding affinity.<ref name= "Siu 2013"/>  Most notably, class B GPCRs contain a <scene name='72/727091/Corticotropin_glucagon_aligned/1'>prominent central splay</scene> which is solvent filled and accessible from the extracellular side.  This central splay is notably absent <scene name='72/727091/B2-adrenergic_glucagon_aligned/9'>from other GPCRs</scene>, and represents a tantalizing target for agonists/antagonists.<ref name= "Hollenstein 2014"/>
 Because of the difficulty in stabilizing and crystallizing Class B TMDs, very little is known about the conformational changes that transduce cell signals endogenously. GCGR is known to regulate additional signal pathways through the adoption of differing receptor conformations and to interact with receptor activity-modifying proteins (RAMPs) altering the signaling bias of the receptor.<ref name= "Xu 2009"/>