Sandbox Reserved 1167: Difference between revisions

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== Glucagon Binding ==

Research has shown that class B GCPRs exist in either an [http://www.nature.com/ncomms/2015/150731/ncomms8859/fig_tab/ncomms8859_F3.html open or closed conformation] differentiating between the receptor's active and inactive states. The active, or open conformation, is characterized by an intracellular outward movement of helicies V and VI (breaking hydrogen bonds between Arg173-~~Ser305~~ and Glu245-Thr351) ''citation needed'' and an extracellular rotation of the ECD until it is almost perpendicular to the membrane surface ''citation needed''. While the stalk region of Helix I helps to facilitate the motion of the ECD, intracellular G-protein coupling and extracellular glucagon binding stabilized this active state. In the abscence of glucagon, however, the GCGR adopts a closed conformation in which all three of the extracellular loops of the 7tm (ECL1, ECL2, and ECL3) can interact with the ECD ''citation needed''. In this closed state, the ECD covers the extracellular surface of the 7tm. To transition between states, the ECD rotates and moves down towards the 7tm domain. This transition mechanism is consistent with the "two-domain" binding mechanism of class B GCPRs in which (1) the C-terminus of the ligand first binds to the ECD allowing (2) the N-terminus of the ligand to interact with the 7tm and activate the protein ''citation needed''.

Research has shown that class B GCPRs exist in either an [http://www.nature.com/ncomms/2015/150731/ncomms8859/fig_tab/ncomms8859_F3.html open or closed conformation] differentiating between the receptor's active and inactive states. The active, or open conformation, is characterized by an intracellular outward movement of helicies V and VI (breaking hydrogen bonds between <scene name='72/721538/Arg173-ser350_h_bond/1'>Arg173-Ser350</scene> and Glu245-Thr351) ''citation needed'' and an extracellular rotation of the ECD until it is almost perpendicular to the membrane surface ''citation needed''. While the stalk region of Helix I helps to facilitate the motion of the ECD, intracellular G-protein coupling and extracellular glucagon binding stabilized this active state. In the abscence of glucagon, however, the GCGR adopts a closed conformation in which all three of the extracellular loops of the 7tm (ECL1, ECL2, and ECL3) can interact with the ECD ''citation needed''. In this closed state, the ECD covers the extracellular surface of the 7tm. To transition between states, the ECD rotates and moves down towards the 7tm domain. This transition mechanism is consistent with the "two-domain" binding mechanism of class B GCPRs in which (1) the C-terminus of the ligand first binds to the ECD allowing (2) the N-terminus of the ligand to interact with the 7tm and activate the protein ''citation needed''.

Sandbox Reserved 1167: Difference between revisions

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Revision as of 05:44, 19 April 2016 view source Alexis Coulis (talk \| contribs) 137 edits No edit summary ← Older edit		Revision as of 05:59, 19 April 2016 view source Alexis Coulis (talk \| contribs) 137 edits No edit summary Newer edit →
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	== Glucagon Binding ==		== Glucagon Binding ==

	Research has shown that class B GCPRs exist in either an [http://www.nature.com/ncomms/2015/150731/ncomms8859/fig_tab/ncomms8859_F3.html open or closed conformation] differentiating between the receptor's active and inactive states. The active, or open conformation, is characterized by an intracellular outward movement of helicies V and VI (breaking hydrogen bonds between Arg173-~~Ser305~~ and Glu245-Thr351) ''citation needed'' and an extracellular rotation of the ECD until it is almost perpendicular to the membrane surface ''citation needed''. While the stalk region of Helix I helps to facilitate the motion of the ECD, intracellular G-protein coupling and extracellular glucagon binding stabilized this active state. In the abscence of glucagon, however, the GCGR adopts a closed conformation in which all three of the extracellular loops of the 7tm (ECL1, ECL2, and ECL3) can interact with the ECD ''citation needed''. In this closed state, the ECD covers the extracellular surface of the 7tm. To transition between states, the ECD rotates and moves down towards the 7tm domain. This transition mechanism is consistent with the "two-domain" binding mechanism of class B GCPRs in which (1) the C-terminus of the ligand first binds to the ECD allowing (2) the N-terminus of the ligand to interact with the 7tm and activate the protein ''citation needed''.		Research has shown that class B GCPRs exist in either an [http://www.nature.com/ncomms/2015/150731/ncomms8859/fig_tab/ncomms8859_F3.html open or closed conformation] differentiating between the receptor's active and inactive states. The active, or open conformation, is characterized by an intracellular outward movement of helicies V and VI (breaking hydrogen bonds between <scene name='72/721538/Arg173-ser350_h_bond/1'>Arg173-Ser350</scene> and Glu245-Thr351) ''citation needed'' and an extracellular rotation of the ECD until it is almost perpendicular to the membrane surface ''citation needed''. While the stalk region of Helix I helps to facilitate the motion of the ECD, intracellular G-protein coupling and extracellular glucagon binding stabilized this active state. In the abscence of glucagon, however, the GCGR adopts a closed conformation in which all three of the extracellular loops of the 7tm (ECL1, ECL2, and ECL3) can interact with the ECD ''citation needed''. In this closed state, the ECD covers the extracellular surface of the 7tm. To transition between states, the ECD rotates and moves down towards the 7tm domain. This transition mechanism is consistent with the "two-domain" binding mechanism of class B GCPRs in which (1) the C-terminus of the ligand first binds to the ECD allowing (2) the N-terminus of the ligand to interact with the 7tm and activate the protein ''citation needed''.