Sandbox Reserved 1703: Difference between revisions

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====G-Protein Recognition====

Transition to the active state also reorients helix lll in both monomers to enable binding to the G-protein: Yet only one chain is required for full receptor activation. The intracellular region of helix lll contributes the main interactions with the alpha subunit of the G-protein. Intracellular Loop 2 also builds a polar interaction network with the G-protein through its ionic interactions with the <scene name='90/904308/Binding_recognition_site/2'> α-subunit</scene> of the G-protein. Lastly, mGlu2 residue E666 forms a salt bridge with ~~an alpha N~~ residue (R32) on the α-subunit which further destabilizes the inactive conformation<ref name="Lin"/>.

Transition to the active state also reorients helix lll in both monomers to enable binding to the G-protein: Yet only one chain is required for full receptor activation. The intracellular region of helix lll contributes the main interactions with the alpha subunit of the G-protein. Intracellular Loop 2 also builds a polar interaction network with the G-protein through its ionic interactions with the <scene name='90/904308/Binding_recognition_site/2'> α-subunit</scene> of the G-protein. Lastly, mGlu2 residue E666 forms a salt bridge with residue (R32) on the α-subunit which further destabilizes the inactive conformation<ref name="Lin"/>.

====G-protein Binding====

The PAM induced downward shift of helix IV coupled with the reorientation of the transmembrane domain to a TM6-TM6 asymmetric interface, opens up a cleft on the intracellular surface of the receptor. This cleft allows a hook-like region (figure 4), from the last 4 terminals of the α-subunit of the G-protein, to move in adjacent to helix IV in the transmembrane domain. Within this interaction, <scene name='90/904308/~~Binding_recognition_site~~/5'>C351</scene> on the hook participates in hydrophobic interactions with Intracellular loop 2 and helix 4. These interactions allow the C-terminal region of the G-protein α-subunit to bind in the shallow groove formed by intracellular loops 2 and 3 and residues on helices 3 and lV<ref name="Lin" />.The receptor is now <scene name='90/904308/Active_structure/3'>fully active</scene> with the dimer coupled only to one G-protein. The ]VFT is in the closed conformation resulting in a tighter form. The TMD helices are also reoriented in both monomers to form an asymmetric dimer interface.

The PAM induced downward shift of helix IV coupled with the reorientation of the transmembrane domain to a TM6-TM6 asymmetric interface, opens up a cleft on the intracellular surface of the receptor. This cleft allows a hook-like region (figure 4), from the last 4 terminals of the α-subunit of the G-protein, to move in adjacent to helix IV in the transmembrane domain. Within this interaction, <scene name='90/904308/Binding_site/4'>C351</scene> on the hook participates in hydrophobic interactions with Intracellular loop 2 and helix 4. These interactions allow the C-terminal region of the G-protein α-subunit to bind in the shallow groove formed by intracellular loops 2 and 3 and residues on helices 3 and lV<ref name="Lin" />.The receptor is now <scene name='90/904308/Active_structure/3'>fully active</scene> with the dimer coupled only to one G-protein. The ]VFT is in the closed conformation resulting in a tighter form. The TMD helices are also reoriented in both monomers to form an asymmetric dimer interface.

==Clinical Relevance==

Sandbox Reserved 1703: Difference between revisions

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@@ Line 33: / Line 33: @@
 ====G-Protein Recognition====
-Transition to the active state also reorients helix lll in both monomers to enable binding to the G-protein: Yet only one chain is required for full receptor activation. The intracellular region of helix lll contributes the main interactions with the alpha subunit of the G-protein. Intracellular Loop 2 also builds a polar interaction network with the G-protein through its ionic interactions with the <scene name='90/904308/Binding_recognition_site/2'> α-subunit</scene> of the G-protein. Lastly, mGlu2 residue E666 forms a salt bridge with an alpha N residue (R32) on the α-subunit which further destabilizes the inactive conformation<ref name="Lin"/>.
+Transition to the active state also reorients helix lll in both monomers to enable binding to the G-protein: Yet only one chain is required for full receptor activation. The intracellular region of helix lll contributes the main interactions with the alpha subunit of the G-protein. Intracellular Loop 2 also builds a polar interaction network with the G-protein through its ionic interactions with the <scene name='90/904308/Binding_recognition_site/2'> α-subunit</scene> of the G-protein. Lastly, mGlu2 residue E666 forms a salt bridge with residue (R32) on the α-subunit which further destabilizes the inactive conformation<ref name="Lin"/>.
 ====G-protein Binding====
-The PAM induced downward shift of helix IV coupled with the reorientation of the transmembrane domain to a TM6-TM6 asymmetric interface, opens up a cleft on the intracellular surface of the receptor. This cleft allows a hook-like region (figure 4), from the last 4 terminals of the α-subunit of the G-protein, to move in adjacent to helix IV in the transmembrane domain. Within this interaction, <scene name='90/904308/Binding_recognition_site/5'>C351</scene> on the hook participates in hydrophobic interactions with Intracellular loop 2 and helix 4. These interactions allow the C-terminal region of the G-protein α-subunit to bind in the shallow groove formed by intracellular loops 2 and 3 and residues on helices 3 and lV<ref name="Lin" />.The receptor is now <scene name='90/904308/Active_structure/3'>fully active</scene> with the dimer coupled only to one G-protein. The ]VFT is in the closed conformation resulting in a tighter form. The TMD helices are also reoriented in both monomers to form an asymmetric dimer interface.
+The PAM induced downward shift of helix IV coupled with the reorientation of the transmembrane domain to a TM6-TM6 asymmetric interface, opens up a cleft on the intracellular surface of the receptor. This cleft allows a hook-like region (figure 4), from the last 4 terminals of the α-subunit of the G-protein, to move in adjacent to helix IV in the transmembrane domain. Within this interaction, <scene name='90/904308/Binding_site/4'>C351</scene> on the hook participates in hydrophobic interactions with Intracellular loop 2 and helix 4. These interactions allow the C-terminal region of the G-protein α-subunit to bind in the shallow groove formed by intracellular loops 2 and 3 and residues on helices 3 and lV<ref name="Lin" />.The receptor is now <scene name='90/904308/Active_structure/3'>fully active</scene> with the dimer coupled only to one G-protein. The ]VFT is in the closed conformation resulting in a tighter form. The TMD helices are also reoriented in both monomers to form an asymmetric dimer interface.
 ==Clinical Relevance==