Glucagon receptor: Difference between revisions
New page: =Glucagon G protein-coupled receptor= <StructureSection load='4l6r' size='350' side='right' caption='Structure of the Class B Human Glucagon G Protein Coupled Receptor-[http://www.rcsb.org... |
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{{BAMBED | |||
|DATE=June 20, 2016 | |||
|OLDID=2609631 | |||
|BAMBEDDOI=10.1002/bmb.21026 | |||
}} | |||
=Glucagon G protein-coupled receptor= | =Glucagon G protein-coupled receptor= | ||
<StructureSection load=' | <StructureSection load='' size='350' side='right' caption='Structure of the Class B Human Glucagon G Protein Coupled Receptor-[http://www.rcsb.org/pdb/home/home.do PDB] [http://www.rcsb.org/pdb/explore/explore.do?structureId=4l6r 4L6R]' scene='72/721536/Class_b_gpcrs/4'> | ||
==Class B GPCRs== | ==Class B GPCRs== | ||
G protein coupled receptors (GPCRs) are the largest class of integral membrane proteins. GPCRs are divided into five families; the rhodopsin family (class A), the secretin family (class B), the glutamate family (class C), the frizzled/taste family (class F), and the adhesion family.<ref name= "Zhang 2006"/> Roughly 5% of the human genome encodes g protein-coupled receptors, which are responsible for the transduction of endogenous signals and the instigation of cellular responses.<ref name= "Zhang 2006"/> All GPCRs contain a similar seven α-helical transmembrane domain <scene name='72/727091/Full_Structure_with_Labels/1'>(TMD or 7TMD)</scene> that once bound to its ligand, undergoes a conformational change and tranduces a signal to coupled, heterotrimeric G proteins. The initiation of intracellular signal pathways occur in response to stimuli such as light, Ca<sup>2+</sup>, amino acids, nucleotides, odorants, peptides, and other proteins, [https://en.wikipedia.org/wiki/G_protein%E2%80%93coupled_receptor#Physiological_roles and accomplishes many interesting physiological roles]. <ref name= "Zhang 2006">DOI 10.1371/journal.pcbi.0020013</ref> The '''human glucagon receptor''' ('''GCGR''') is one of 15 secretin-like, or Class B, [https://en.wikipedia.org/wiki/G_protein%E2%80%93coupled_receptor G-protein coupled receptors] (GPCRs). Like other GPCRs, it has a <scene name='72/721538/7tm_labeled_helicies/3'>7 trans-membrane </scene> helical domain and a globular N-terminus <scene name='72/721538/Ecd/2'>extracellular domain</scene> (ECD). [[Image:Protter GLR HUMAN.png |250 px|left|thumb|'''Figure 1''': Snake Plot of GCGR TMD. Residues of particular importance in glucagon binding affinity are found in green, yellow, and black. Residues in red are the location of critical disulfide bonds, while blue residues were found to be highly conserved across all class B GPCRs.<ref name= "Siu 2013"/>]] | [[G protein-coupled receptors]] (GPCRs) are the largest class of integral membrane proteins. GPCRs are divided into five families; the rhodopsin family (class A), the secretin family (class B), the glutamate family (class C), the frizzled/taste family (class F), and the adhesion family.<ref name= "Zhang 2006"/> Roughly 5% of the human genome encodes g protein-coupled receptors, which are responsible for the transduction of endogenous signals and the instigation of cellular responses.<ref name= "Zhang 2006"/> All GPCRs contain a similar seven α-helical transmembrane domain <scene name='72/727091/Full_Structure_with_Labels/1'>(TMD or 7TMD)</scene> that once bound to its ligand, undergoes a conformational change and tranduces a signal to coupled, heterotrimeric G proteins. The initiation of intracellular signal pathways occur in response to stimuli such as light, Ca<sup>2+</sup>, amino acids, nucleotides, odorants, peptides, and other proteins, [https://en.wikipedia.org/wiki/G_protein%E2%80%93coupled_receptor#Physiological_roles and accomplishes many interesting physiological roles]. <ref name= "Zhang 2006">DOI 10.1371/journal.pcbi.0020013</ref> The '''human glucagon receptor''' ('''GCGR''') is one of 15 secretin-like, or Class B, [https://en.wikipedia.org/wiki/G_protein%E2%80%93coupled_receptor G-protein coupled receptors] (GPCRs). Like other GPCRs, it has a <scene name='72/721538/7tm_labeled_helicies/3'>7 trans-membrane </scene> helical domain and a globular N-terminus <scene name='72/721538/Ecd/2'>extracellular domain</scene> (ECD). [[Image:Protter GLR HUMAN.png |250 px|left|thumb|'''Figure 1''': Snake Plot of GCGR TMD. Residues of particular importance in glucagon binding affinity are found in green, yellow, and black. Residues in red are the location of critical disulfide bonds, while blue residues were found to be highly conserved across all class B GPCRs.<ref name= "Siu 2013"/>]] | ||
Class B GPCRs contain 15 distinct receptors for peptide hormones and generate their signal pathway through the activation of adenylate cyclase (AC) which increases the intracellular concentration of cAMP, inositol phosphate, and calcium levels. <ref>DOI 10.1111/bph.12689</ref> These secondary messengers are essential elements of intracellular signal cascades for human diseases including type II diabetes mellitus, osteoporosis, obesity, cancer, neurological degeneration, cardiovascular diseases, headaches, and psychiatric disorders; making their regulation through drug targeting of particular interest as disease targets. <ref name= "Hollenstein 2014">DOI 10.1016/j.tips.2013.11.001</ref> Structural approaches to the development of agonists and antagonists have however been hampered by the lack of accurate Class B TMD visualizations. Recent crystal structures of corticoptropin-releasing factor receptor 1 (PDB: 4K5Y) and human glucagon receptor (PDB: 4L6R) provide a comparison to more well-studied class A GPCRs. <ref name= "Hollenstein 2013">DOI 10.1038/nature12357</ref><ref name= "Siu 2013">DOI 10.1038/nature12393</ref> | Class B GPCRs contain 15 distinct receptors for peptide hormones and generate their signal pathway through the activation of adenylate cyclase (AC) which increases the intracellular concentration of cAMP, inositol phosphate, and calcium levels. <ref>DOI 10.1111/bph.12689</ref> These secondary messengers are essential elements of intracellular signal cascades for human diseases including type II diabetes mellitus, osteoporosis, obesity, cancer, neurological degeneration, cardiovascular diseases, headaches, and psychiatric disorders; making their regulation through drug targeting of particular interest as disease targets. <ref name= "Hollenstein 2014">DOI 10.1016/j.tips.2013.11.001</ref> Structural approaches to the development of agonists and antagonists have however been hampered by the lack of accurate Class B TMD visualizations. Recent crystal structures of corticoptropin-releasing factor receptor 1 (PDB: 4K5Y) and human glucagon receptor (PDB: 4L6R) provide a comparison to more well-studied class A GPCRs. <ref name= "Hollenstein 2013">DOI 10.1038/nature12357</ref><ref name= "Siu 2013">DOI 10.1038/nature12393</ref> | ||
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[https://en.wikipedia.org/wiki/G_protein%E2%80%93coupled_receptor G protein-coupled receptors] | [https://en.wikipedia.org/wiki/G_protein%E2%80%93coupled_receptor G protein-coupled receptors] | ||
Linked pages of related receptors (co-featured in BAMBED): | |||
*[[GPR40]] | |||
*[[Lysophosphatidic acid receptor]] | |||
*[[Metabotropic glutamate receptor 5]] | |||
*[[Neurotensin receptor]] | |||
==Proteopedia Resources== | ==Proteopedia Resources== | ||
[ | [[Glucagon]] | ||
[[G protein-coupled receptor]] | |||
[http://proteopedia.org/wiki/index.php/Category:Glucagon_receptor Category:Glucagon Receptor] | [http://proteopedia.org/wiki/index.php/Category:Glucagon_receptor Category:Glucagon Receptor] | ||
[http://proteopedia.org/wiki/index.php/User:R._Jeremy_Johnson/CH462:Biochemistry_II_Butler_University Butler University Proteopedia Pages] | [http://proteopedia.org/wiki/index.php/User:R._Jeremy_Johnson/CH462:Biochemistry_II_Butler_University Butler University Proteopedia Pages] | ||
*[[Receptor]] | |||
*[[Transmembrane (cell surface) receptors]] | |||
==3D structures of glucagon receptor== | |||
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | |||
[[5ee7]] - hGCGR + antagonist - human<br /> | |||
[[7s15]] - hGCGR + agonist <br /> | |||
[[4ers]] - hGCGR + antibody<br /> | |||
[[4lf3]] - hGCGR (mutant) + antibody<br /> | |||
[[5xez]], [[5xf1]] – hGCGR/endolysin + antibody<br /> | |||
[[5yqz]] – hGCGR/endolysin + glucagon peptide <br /> | |||
[[6lmk]] - hGCGR + guanine nucleotide-binding protein + NB35 + glucagon peptide – Cryo EM<br /> | |||
[[6lml]], [[7v35]] - hGCGR + guanine nucleotide-binding protein + Scfv16 + glucagon peptide – Cryo EM<br /> | |||
[[6whc]] - hGCGR + guanine nucleotide-binding protein + nanobody + dual-agonist peptide – Cryo EM<br /> | |||
[[6wpw]] - hGCGR + guanine nucleotide-binding protein + NB35 + glucagon derivative – Cryo EM<br /> | |||
</StructureSection> | </StructureSection> | ||
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Dean Williams | Dean Williams | ||
[[Category:Featured in BAMBED]] | |||
[[Category:Topic Page]] | |||
[[Category:G protein-coupled receptor]] | |||