Sandbox Reserved 1160: Difference between revisions

Line 30:

=== Ionic Locks ===

Another important structural feature is the series of <scene name='72/721531/Ionic_lock/5'>ionic locks</scene> on the intracellular side of the protein. Interactions between these five amino acids will form a salt bridge, which will stabilize the inactive conformation<ref name="Dore" />. The primary ionic lock forms between Glu770, Lys665, and Ser613<ref name="Dore" />. A secondary ionic lock occurs between Ser614 and Arg668<ref name="Dore" />. The purpose of these ionic locks is analogous to the ionic interactions that stabilize the T state in [[Hemoglobin]]. In the case of the TMD of mGlu5, the ionic lock is formed when the NAM mavoglurant is bound. ~~This~~ ionic ~~lock stabilizes~~ the inactive state, where the intracellular loops are stabilized facing inwards<ref name="Wu" />. This conformational change will effectively block the crevice that is involved in binding the G-protein<ref name="Wu" />. Models have suggested that, even in a glutamate bound state, the mavoglurant bound receptor would be dimerized but incapable of signaling<ref name="Wu" />. This signaling incapable mGlu5 dimer will help maintain the readiness of the pathway, while still decreasing signal response.

Another important structural feature is the series of <scene name='72/721531/Ionic_lock/5'>ionic locks</scene> on the intracellular side of the protein. Interactions between these five amino acids will form a salt bridge, which will stabilize the inactive conformation<ref name="Dore" />. The primary ionic lock forms between Glu770, Lys665, and Ser613<ref name="Dore" />. A secondary ionic lock occurs between Ser614 and Arg668<ref name="Dore" />. The purpose of these ionic locks is analogous to the ionic interactions that stabilize the T state in [[Hemoglobin]]. In the case of the TMD of mGlu5, the ionic lock is formed when the NAM mavoglurant is bound. These <scene name='72/721531/Ionic_lock/5'>ionic locks</scene> stabilize the inactive state, where the intracellular loops are stabilized facing inwards<ref name="Wu" />. This conformational change will effectively block the crevice that is involved in binding the G-protein<ref name="Wu" />. Models have suggested that, even in a glutamate bound state, the mavoglurant bound receptor would be dimerized but incapable of signaling<ref name="Wu" />. This signaling incapable mGlu5 dimer will help maintain the readiness of the pathway, while still decreasing signal response.

== Disease ==

Sandbox Reserved 1160: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 30: / Line 30: @@
 === Ionic Locks ===
-Another important structural feature is the series of <scene name='72/721531/Ionic_lock/5'>ionic locks</scene> on the intracellular side of the protein. Interactions between these five amino acids will form a salt bridge, which will stabilize the inactive conformation<ref name="Dore" />. The primary ionic lock forms between Glu770, Lys665, and Ser613<ref name="Dore" />. A secondary ionic lock occurs between Ser614 and Arg668<ref name="Dore" />. The purpose of these ionic locks is analogous to the ionic interactions that stabilize the T state in [[Hemoglobin]]. In the case of the TMD of mGlu5,  the ionic lock is formed when the NAM mavoglurant is bound. This ionic lock stabilizes the inactive state, where the intracellular loops are stabilized facing inwards<ref name="Wu" />. This conformational change will effectively block the crevice that is involved in binding the G-protein<ref name="Wu" />. Models have suggested that, even in a glutamate bound state, the mavoglurant bound receptor would be dimerized but incapable of signaling<ref name="Wu" />. This signaling incapable mGlu5 dimer will help maintain the readiness of the pathway, while still decreasing signal response.
+Another important structural feature is the series of <scene name='72/721531/Ionic_lock/5'>ionic locks</scene> on the intracellular side of the protein. Interactions between these five amino acids will form a salt bridge, which will stabilize the inactive conformation<ref name="Dore" />. The primary ionic lock forms between Glu770, Lys665, and Ser613<ref name="Dore" />. A secondary ionic lock occurs between Ser614 and Arg668<ref name="Dore" />. The purpose of these ionic locks is analogous to the ionic interactions that stabilize the T state in [[Hemoglobin]]. In the case of the TMD of mGlu5,  the ionic lock is formed when the NAM mavoglurant is bound. These <scene name='72/721531/Ionic_lock/5'>ionic locks</scene> stabilize the inactive state, where the intracellular loops are stabilized facing inwards<ref name="Wu" />. This conformational change will effectively block the crevice that is involved in binding the G-protein<ref name="Wu" />. Models have suggested that, even in a glutamate bound state, the mavoglurant bound receptor would be dimerized but incapable of signaling<ref name="Wu" />. This signaling incapable mGlu5 dimer will help maintain the readiness of the pathway, while still decreasing signal response.
 == Disease ==