Sandbox Reserved 1167: Difference between revisions
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== Function == | == Function == | ||
The glucagon receptor plays an important role in glucose homeostasis. During times of fasting (or low blood sugar) the pancreas produces glucagon to activate the GCGR in the liver. The [http://www.nature.com/nature/journal/v499/n7459/fig_tab/nature12393_F5.html binding of glucagon] | The glucagon receptor plays an important role in glucose homeostasis. During times of fasting (or low blood sugar) the pancreas produces glucagon to activate the GCGR in the liver. The [http://www.nature.com/nature/journal/v499/n7459/fig_tab/nature12393_F5.html binding of glucagon] to the extracellular side of GCGR leads to the activation of the receptor. On the intracellular side, upon this activation, a guanine diphosphate (GDP) is exchanged for a guanine triphosphate (GTP) - which, in turn, activates adenylate cyclase. Converting adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP), adenylate cyclase initiates protein kinase A (PKA) activity, which releases glucose into the blood stream. Overall, activation of the GCGR elevates blood sugar levels. | ||
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However, one particular difference between class A receptors and class B receptors is an inward shift of the intracellular component of Helix VII. In class A receptors this inward shift is instrumental in receptor activation, yet in class B receptors it remains unclear what role this shift plays<ref name ='structure_article'>PMID:23863937</ref>. | However, one particular difference between class A receptors and class B receptors is an inward shift of the intracellular component of Helix VII. In class A receptors this inward shift is instrumental in receptor activation, yet in class B receptors it remains unclear what role this shift plays<ref name ='structure_article'>PMID:23863937</ref>. | ||
In contrast to class A glucagon receptors which have a [https://en.wikipedia.org/wiki/Proline proline] kink, in all [https://en.wikipedia.org/wiki/Secretin_receptor_family secretin-like class B glucagon receptors] a [https://en.wikipedia.org/wiki/Glycine Glycine] at position 393 in Helix VII allows for a <scene name='72/721537/Gly_393_helical_bend/ | In contrast to class A glucagon receptors which have a [https://en.wikipedia.org/wiki/Proline proline] kink, in all [https://en.wikipedia.org/wiki/Secretin_receptor_family secretin-like class B glucagon receptors] a [https://en.wikipedia.org/wiki/Glycine Glycine] at position 393 in Helix VII allows for a <scene name='72/721537/Gly_393_helical_bend/3'>helical bend</scene>. This glycine helical bend is fully [https://en.wikipedia.org/wiki/Conserved_sequence conserved] in all secretin-like class B receptors. | ||
Another important structural component found in all secretin-like class B receptors are the two conserved [https://en.wikipedia.org/wiki/Salt_bridge_%28protein_and_supramolecular%29 salt bridges] found between [https://en.wikipedia.org/wiki/Arginine Arg] 346 and [https://en.wikipedia.org/wiki/Glutamic_acid Glu] 406 and Arg 173 and Glu 406 | Another important structural component found in all secretin-like class B receptors are the two conserved [https://en.wikipedia.org/wiki/Salt_bridge_%28protein_and_supramolecular%29 salt bridges] found between [https://en.wikipedia.org/wiki/Arginine Arg] 346 and [https://en.wikipedia.org/wiki/Glutamic_acid Glu] 406 and Arg 173 and Glu 406. These <scene name='72/721537/Salt_bridges/2'>salt bridges</scene> are a distinct feature of class B receptors because their interaction results in the distinct stalk found only in class B receptors<ref name ='structure_article'>PMID:23863937</ref>. | ||
While interface interactions between helices VI, V, and III, are not unique to class B receptors because certain homologous and even conserved residues exist in class A receptors (like [https://en.wikipedia.org/wiki/Tyrosine Tyr] 239 and Leu 358), as a part of the interface <scene name='72/721537/Helical_interactions_vi-v-iii/2'>stabilization</scene> between helices VI, V, and III, a Class B-specific [https://en.wikipedia.org/wiki/Hydrogen_bond hydrogen bond] occurs between [https://en.wikipedia.org/wiki/Asparagine Asn] 318 of Helix V and [https://en.wikipedia.org/wiki/Leucine Leu] 242 of Helix III <ref name ='structure_article'>PMID:23863937</ref>. | |||
=== GCGR-Specific Traits === | === GCGR-Specific Traits === | ||
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====Other Unique Structural Features ==== | ====Other Unique Structural Features ==== | ||
An important interface stabilization interaction between Helices I and VII occurs between [https://en.wikipedia.org/wiki/Serine Ser] 152 of Helix I and Ser 390 of Helix VII. Due to their close proximity to one another, they form an important <scene name='72/721537/Ser-ser_hydrogen_bond/ | An important interface stabilization interaction between Helices I and VII occurs between [https://en.wikipedia.org/wiki/Serine Ser] 152 of Helix I and Ser 390 of Helix VII. Due to their close proximity to one another, they form an important <scene name='72/721537/Ser-ser_hydrogen_bond/3'>hydrogen bond</scene> which stabilizes the structure of GCGR. Mutations to the homologous residues Ser 135 and Ser 392 have been shown to alter receptor signaling in [https://en.wikipedia.org/wiki/Glucagon-like_peptide_1_receptor glucagon-like peptide-1 receptor] (GLP1R). | ||
