Sandbox Reserved 1167: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 9: | Line 9: | ||
== Function == | == Function == | ||
The glucagon receptor plays an important role in glucose homeostasis. During times of fasting (or low blood sugar) the pancreas | 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] stimulates [https://en.wikipedia.org/wiki/Gluconeogenesis gluconeogenesis], through [https://en.wikipedia.org/wiki/Adenylyl_cyclase adenylate cyclase] that initiates [https://en.wikipedia.org/wiki/Protein_kinase_A protein kinase A] (PKA) activity<ref>PMID:25674162</ref>. This pathway synthesizes glucose, elevating blood sugar levels. | ||
| Line 16: | Line 16: | ||
=== Class B vs. Class A === | === Class B vs. Class A === | ||
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] | Like all classes of glucagon receptors, which include class A ([https://en.wikipedia.org/wiki/Rhodopsin-like_receptors rhodopsin-like]), B (secretin-like), and [https://en.wikipedia.org/wiki/Class_C_GPCR C] ([https://en.wikipedia.org/wiki/Metabotropic_glutamate_receptor metabotropic glutamate]), GCGR has a 7tm domain. While class B receptors do share characteristics with class C receptors, they are more similar to class A receptors. Class B receptors and class A receptors share less than 15% sequence [https://en.wikipedia.org/wiki/Homology_(biology) homology]; however, they do share similar [https://en.wikipedia.org/wiki/Signal_transduction signal transduction] mechanisms as well as the 7tm domain. The orientations and positions of the 7tm helices are also conserved between both classes of glucagon receptors. | ||
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. | |||
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/1'>helical bend</scene>. This glycine helical bend is fully [https://en.wikipedia.org/wiki/Conserved_sequence conserved] in all secretin-like class B receptors and is an important part of the FQGxxVxxYCF [https://en.wikipedia.org/wiki/Sequence_motif motif]. | |||
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 [[Image:Salt Bridge Interactions.png | 250 px|right|thumb|Glu 406 Salt Bridges]]. These salt bridges are a distinct feature of class B receptors only because their interaction results in the distinct stalk found only in class B receptors<ref name ='structure_article'>PMID:23863937</ref>. | 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 [[Image:Salt Bridge Interactions.png | 250 px|right|thumb|Glu 406 Salt Bridges]]. These salt bridges are a distinct feature of class B receptors only because their interaction results in the distinct stalk found only in class B receptors<ref name ='structure_article'>PMID:23863937</ref>. | ||
