Sandbox Reserved 1649: Difference between revisions

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'''Transmembrane domain'''

The transmembrane domain is organized into '''4 parts''' (from M1 to M4). M1 connects the N-terminal domain to M2. M2 forms a reentrant loop contributing to the pore. The S1 segment of the N-terminal domain intertwines with the S2 segment of the GlnBP-type domain in the extracellular loop M3 - M4 to form the glutamate binding pocket. On the other hand, desensitization of NMDA receptors is affected by residues near or inside the binding pocket as well as by residues in M2 that line the pore and the M3 loop - M4 is not responsible for the specificity of the NR2 subunit of glycine independent desensitization. <ref name="transmembrane domain">DOI 10.1016/S0896-6273(00)80459-6</ref>

The transmembrane domain is organized into '''4 parts''' (from M1 to M4). '''M1''' connects the N-terminal domain to M2. '''M2''' forms a reentrant loop contributing to the pore. The '''S1''' segment of the N-terminal domain '''intertwines with the S2 segment''' of the GlnBP-type domain in the extracellular loop '''M3 - M4''' to form the '''glutamate''' binding pocket. On the other hand, desensitization of NMDA receptors is affected by residues near or inside the binding pocket as well as by residues in M2 that line the pore and the M3 loop - M4 is not responsible for the specificity of the NR2 subunit of glycine independent desensitization. <ref name="transmembrane domain">DOI 10.1016/S0896-6273(00)80459-6</ref>

M2 loop is a channel-lining loop and located in transmembrane domain. Two [https://en.wikipedia.org/wiki/Asparagine asparagines] are located on N site of the domain and block Mg2+ and are permeable of Ca2+ <ref name="M2loop">DOI 10.3390/ijms21041538</ref>

Structurally, there is a small loop of 150 amino acids between M3 and M4. Ethanol acts as an inhibitor on NMDAr. [https://en.wikipedia.org/wiki/Phenylalanine phenylalanine] at position 639 in the M3 part of the transmembrane domain of NR2A interacts with the latter.<ref name="ethanol inhibition">DOI 10.1074 / jbc.M102800200</ref>

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'''CTD'''

CTD domain is the less conserved of the NR2 domains. Like ATD, it allows different localization of NMDAr thanks to reticulum endoplasmic trafficking. It is indispensable for receptor surface dynamic and activation of specific signaling. CTD phosphorylation can modulate NMDAr, for instance it is useful for endocytosis during glutamate binding on LBD. <ref name="M2loop"/>

CTD domain is the '''less conserved''' of the NR2 domains. Like ATD, it allows different localization of NMDAr thanks to reticulum endoplasmic trafficking. It is indispensable for receptor surface dynamic and activation of specific signaling. CTD phosphorylation can modulate NMDAr, for instance it is useful for endocytosis during glutamate binding on LBD. <ref name="M2loop"/>

== Regulation ==

A high quantity of stress can lead to the '''overactivation of NMDA receptors'''. Therefore, a regulation can occur on NMDA receptors in order to avoid any neuronal injury. <ref name="Structural Rearrangements of NR1/NR2A NMDA Receptors during Allosteric Inhibition">DOI 10.1016/j.neuron.2010.08.011</ref> This very important regulation can act at the level of NR2A subunit.

A '''high quantity of stress''' can lead to the '''overactivation of NMDA receptors'''. Therefore, a regulation can occur on NMDA receptors in order to avoid any neuronal injury. <ref name="Structural Rearrangements of NR1/NR2A NMDA Receptors during Allosteric Inhibition">DOI 10.1016/j.neuron.2010.08.011</ref> This very important regulation can act at the level of NR2A subunit.

For now, scientists know that regulation can occur in several ways: either a modification directly affects the functioning of the receptor, or the quantity of receptors at the surface of the neuron by modifying NR2A itself or not.

Sandbox Reserved 1649: Difference between revisions

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@@ Line 42: / Line 42: @@
 '''Transmembrane domain'''
-The transmembrane domain is organized into '''4 parts''' (from M1 to M4). M1 connects the N-terminal domain to M2. M2 forms a reentrant loop contributing to the pore. The S1 segment of the N-terminal domain intertwines with the S2 segment of the GlnBP-type domain in the extracellular loop M3 - M4 to form the glutamate binding pocket. On the other hand, desensitization of NMDA receptors is affected by residues near or inside the binding pocket as well as by residues in M2 that line the pore and the M3 loop - M4 is not responsible for the specificity of the NR2 subunit of glycine independent desensitization. <ref name="transmembrane domain">DOI 10.1016/S0896-6273(00)80459-6</ref>
+The transmembrane domain is organized into '''4 parts''' (from M1 to M4). '''M1''' connects the N-terminal domain to M2. '''M2''' forms a reentrant loop contributing to the pore. The '''S1''' segment of the N-terminal domain '''intertwines with the S2 segment''' of the GlnBP-type domain in the extracellular loop '''M3 - M4''' to form the '''glutamate''' binding pocket. On the other hand, desensitization of NMDA receptors is affected by residues near or inside the binding pocket as well as by residues in M2 that line the pore and the M3 loop - M4 is not responsible for the specificity of the NR2 subunit of glycine independent desensitization. <ref name="transmembrane domain">DOI 10.1016/S0896-6273(00)80459-6</ref>
 M2 loop is a channel-lining loop and located in transmembrane domain. Two [https://en.wikipedia.org/wiki/Asparagine asparagines] are located on N site of the domain and block Mg2+ and are permeable of Ca2+ <ref name="M2loop">DOI 10.3390/ijms21041538</ref>
 Structurally, there is a small loop of 150 amino acids between M3 and M4. Ethanol acts as an inhibitor on NMDAr. [https://en.wikipedia.org/wiki/Phenylalanine phenylalanine] at position 639 in the M3 part of the transmembrane domain of NR2A interacts with the latter.<ref name="ethanol inhibition">DOI 10.1074 / jbc.M102800200</ref>
@@ Line 48: / Line 48: @@
 '''CTD'''
-CTD domain is the less conserved of the NR2 domains. Like ATD, it allows different localization of NMDAr thanks to reticulum endoplasmic trafficking. It is indispensable for receptor surface dynamic and activation of specific signaling. CTD phosphorylation can modulate NMDAr, for instance it is useful for endocytosis during glutamate binding on LBD. <ref name="M2loop"/>
+CTD domain is the '''less conserved''' of the NR2 domains. Like ATD, it allows different localization of NMDAr thanks to reticulum endoplasmic trafficking. It is indispensable for receptor surface dynamic and activation of specific signaling. CTD phosphorylation can modulate NMDAr, for instance it is useful for endocytosis during glutamate binding on LBD. <ref name="M2loop"/>
 == Regulation ==
-A high quantity of stress can lead to the '''overactivation of NMDA receptors'''. Therefore, a regulation can occur on NMDA receptors in order to avoid any neuronal injury. <ref name="Structural Rearrangements of NR1/NR2A NMDA Receptors during Allosteric Inhibition">DOI 10.1016/j.neuron.2010.08.011</ref> This very important regulation can act at the level of NR2A subunit.
+A '''high quantity of stress''' can lead to the '''overactivation of NMDA receptors'''. Therefore, a regulation can occur on NMDA receptors in order to avoid any neuronal injury. <ref name="Structural Rearrangements of NR1/NR2A NMDA Receptors during Allosteric Inhibition">DOI 10.1016/j.neuron.2010.08.011</ref> This very important regulation can act at the level of NR2A subunit.
 For now, scientists know that regulation can occur in several ways: either a modification directly affects the functioning of the receptor, or the quantity of receptors at the surface of the neuron by modifying NR2A itself or not.