Sandbox Reserved 1165: Difference between revisions
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==How These Structures Lead to Function== | ==How These Structures Lead to Function== | ||
Structurally, the 7TM and its signature seven helical structure is involved in [https://en.wikibooks.org/wiki/Principles_of_Biochemistry/Signaling_inside_the_Cell signaling] via [https://en.wikibooks.org/wiki/Structural_Biochemistry/Energy_coupling_in_chemical_reactions coupling] to [https://en.wikipedia.org/wiki/Heterotrimeric_G_protein heterotrimeric G proteins] that activate [https://en.wikipedia.org/wiki/Adenylyl_cyclase adenylate cyclase] to increase the levels of intracellular [https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate cyclic AMP]. Additionally, this coupling increases levels of [https://en.wikipedia.org/wiki/Inositol_phosphate IP3] and intracellular [https://en.wikipedia.org/wiki/Calcium calcium] levels. <ref name="Tips">PMID: 23863937</ref> The wider and deeper ligand-binding pocket of class B GPCRs allows for a vast array of molecules to be bound that in turn allow for numerous functions activated by peptide [https://en.wikipedia.org/wiki/Receptor_(biochemistry) receptors]. <ref name="Ligands">PMID: 21542831</ref> The conformation and orientation of the 7TM and the ECD regions dictate the functionality of the class B G protein-coupled receptor, which has an open and closed [https://en.wikipedia.org/wiki/Conformation conformation] of the GCGR. When glucagon binds to GCGR, the open conformation of GCGR is stabilized. | Structurally, the 7TM and its signature seven helical structure is involved in [https://en.wikibooks.org/wiki/Principles_of_Biochemistry/Signaling_inside_the_Cell signaling] via [https://en.wikibooks.org/wiki/Structural_Biochemistry/Energy_coupling_in_chemical_reactions coupling] to [https://en.wikipedia.org/wiki/Heterotrimeric_G_protein heterotrimeric G proteins] that activate [https://en.wikipedia.org/wiki/Adenylyl_cyclase adenylate cyclase] to increase the levels of intracellular [https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate cyclic AMP]. Additionally, this coupling increases levels of [https://en.wikipedia.org/wiki/Inositol_phosphate IP3] and intracellular [https://en.wikipedia.org/wiki/Calcium calcium] levels. <ref name="Tips">PMID: 23863937</ref> The wider and deeper ligand-binding pocket of class B GPCRs allows for a vast array of molecules to be bound that in turn allow for numerous functions activated by peptide [https://en.wikipedia.org/wiki/Receptor_(biochemistry) receptors]. <ref name="Ligands">PMID: 21542831</ref> The conformation and orientation of the 7TM and the ECD regions dictate the functionality of the class B G protein-coupled receptor, which has an open and closed [https://en.wikipedia.org/wiki/Conformation conformation] of the GCGR. When glucagon binds to GCGR, the open conformation of GCGR is stabilized. The open conformation is when glucagon can bind to GCGR; in the closed conformation binding does not occur.<ref name="Ligands">PMID: 21542831</ref> | ||
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There are specific amino acid interactions that hold the helices of the 7TM in the conformation that maximizes [http://www.chemicool.com/definition/affinity.html affinity]. <ref name="Ligands">PMID: 21542831</ref> This includes the [https://en.wikipedia.org/wiki/Disulfide disulfide bond] between <scene name='72/721535/Disulfide_bond_notspin/1'> Cys 294 and Cys 224</scene> that serves to hold the helices in the proper orientation for binding. Additionally, the [https://en.wikipedia.org/wiki/Salt_bridge_%28protein_and_supramolecular%29 salt bridges] between Glu 406, Arg 173, and Arg 346, also mentioned earlier, hold the conformation together for higher affinity (Figure 3). <ref name="Ligands">PMID: 21542831</ref> Finally, alpha helical structure of the stalk is | There are specific amino acid interactions that hold the helices of the 7TM in the conformation that maximizes [http://www.chemicool.com/definition/affinity.html affinity]. <ref name="Ligands">PMID: 21542831</ref> This includes the [https://en.wikipedia.org/wiki/Disulfide disulfide bond] between <scene name='72/721535/Disulfide_bond_notspin/1'> Cys 294 and Cys 224</scene> that serves to hold the helices in the proper orientation for binding. Additionally, the [https://en.wikipedia.org/wiki/Salt_bridge_%28protein_and_supramolecular%29 salt bridges] between Glu 406, Arg 173, and Arg 346, also mentioned earlier, hold the conformation together for higher affinity (Figure 3). <ref name="Ligands">PMID: 21542831</ref> Finally, alpha helical structure of the <scene name='72/721535/Opening_orientation/2'>stalk</scene> is required for high affinity conformation. The high affinity conformation of GCGR is the open conformation when glucagon can bind. Without these specific interactions between the residues open conformation is not stabilized and GCGR remains in the closed conformation where glucagon cannot bind. <ref name="Tips">PMID: 23863937</ref> | ||
