Sandbox42: Difference between revisions

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== '''Overall Structure''' ==

To date, the entire X-ray or NMR crystal structure of the <scene name='Sandbox42/Initial/1'>NMDA receptor</scene> has not been produced. However, there are many structural subunits of NMDA that have successfully been crystallized and analyzed which provide some structural information about the NMDA receptor. The architecture of NMDA receptors is modular and is composed of multiple domains with distinct functional roles. The large extracellular region of the receptor is partitioned into two domains: an <scene name='Sandbox42/Atd/1'>amino-terminal domain</scene> (ATD) and a <scene name='Sandbox42/Lbd/2'>ligand-binding domain</scene> (LBD) (6). Each domain consists of 8 <scene name='Sandbox42/Alpha/2'>alpha helices</scene> and antiparallel <scene name='Sandbox42/Beta/4'>beta sheets</scene>. The alpha helices are located on the outside while the beta sheets are found more toward the center. The NMDA receptor has polar amino acid side-chains located extracellularly and at the ion-pore, but also many non-polar side chains at points where the protein passes through the phospholipid bilayer.

To date, the entire X-ray or NMR crystal structure of the <scene name='Sandbox42/Initial/1'>NMDA receptor</scene> has not been produced. However, there are many structural subunits of NMDA that have successfully been crystallized and analyzed which provide some structural information about the NMDA receptor. The architecture of NMDA receptors is modular and is composed of multiple domains with distinct functional roles. The large extracellular region of the receptor is partitioned into two domains: an <scene name='Sandbox42/Atd/1'>amino-terminal domain</scene> (ATD) and a <scene name='Sandbox42/Lbd/2'>ligand-binding domain</scene> (LBD) (7). Each domain consists of 8 <scene name='Sandbox42/Alpha/2'>alpha helices</scene> and antiparallel <scene name='Sandbox42/Beta/4'>beta sheets</scene>. The alpha helices are located on the outside while the beta sheets are found more toward the center. The NMDA receptor has polar amino acid side-chains located extracellularly and at the ion-pore, but also many non-polar side chains at points where the protein passes through the phospholipid bilayer.

The ligand-binding domain of NMDA receptors are heterotetrameric ion channels composed of two copies of the glycine-binding NR1 subunit and two copies of the L-glutamate-binding NR2 subunit. The NR1 subunit is further divided up into splice units while the NR2 subunit has four sub-variants (NR2A-NR2D). The receptor as a whole has four general ligand binding sites (7).

The ligand-binding domain of NMDA receptors are heterotetrameric ion channels composed of two copies of the glycine-binding NR1 subunit and two copies of the L-glutamate-binding NR2 subunit. The NR1 subunit is further divided up into splice units while the NR2 subunit has four sub-variants (NR2A-NR2D). The receptor as a whole has four general ligand binding sites (8).

The amino-terminal domain has an overall clamshell shaped structure and is notably distinct from non-NMDA receptor ATD's. The most important ATD is the NR2B ATD and it is particularly important in current research. It has been shown that the binding of Zn2+ provides neuroprotective agents without the adverse side effects that are more commonly observed with LBD agonists. NR2B ATD has the typical clamshell-like architecture composed of two domains, R1 and R2, which are tied together by three well-structured loops. There is a distinct R1–R2 domain orientation, which in NR2B ATD, is ‘twisted’ by a striking rotation of B45 and 541 compared with the R1–R2 orientation in GluR2 ATD or GluR6 ATD (6).

The amino-terminal domain has an overall clamshell shaped structure and is notably distinct from non-NMDA receptor ATD's. The most important ATD is the NR2B ATD and it is particularly important in current research. It has been shown that the binding of Zn2+ provides neuroprotective agents without the adverse side effects that are more commonly observed with LBD agonists. NR2B ATD has the typical clamshell-like architecture composed of two domains, R1 and R2, which are tied together by three well-structured loops. There is a distinct R1–R2 domain orientation, which in NR2B ATD, is ‘twisted’ by a striking rotation of B45 and 541 compared with the R1–R2 orientation in GluR2 ATD or GluR6 ATD (7).

There are three types of sub units of an NMDA receptor, but not all receptors have the same composition of subtypes. Each subunit consists of three transmembrane segments, a P loop, and an intracellular C-terminus domain (CTD). The segments S1 and S2 in the LBD form a venus-flytrap structure and define the region for agonist recognition (7).

There are three types of sub units of an NMDA receptor, but not all receptors have the same composition of subtypes. Each subunit consists of three transmembrane segments, a P loop, and an intracellular C-terminus domain (CTD). The segments S1 and S2 in the LBD form a venus-flytrap structure and define the region for agonist recognition (8).

The first molecule is the closed NMDA receptor in its natural state. The second is the open NMDA receptor when it is bound by glutamate and co-agonist glycine. The third is the closed form of the NR2B subunit when it is bound by Zn2+. The fourth is the open state of the NR2B subunit.

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@@ Line 27: / Line 27: @@
 == '''Overall Structure''' ==
-To date, the entire X-ray or NMR crystal structure of the <scene name='Sandbox42/Initial/1'>NMDA receptor</scene> has not been produced. However, there are many structural subunits of NMDA that have successfully been crystallized and analyzed which provide some structural information about the NMDA receptor. The architecture of NMDA receptors is modular and is composed of multiple domains with distinct functional roles. The large extracellular region of the receptor is partitioned into two domains: an <scene name='Sandbox42/Atd/1'>amino-terminal domain</scene> (ATD) and a <scene name='Sandbox42/Lbd/2'>ligand-binding domain</scene> (LBD) (6). Each domain consists of 8 <scene name='Sandbox42/Alpha/2'>alpha helices</scene> and antiparallel <scene name='Sandbox42/Beta/4'>beta sheets</scene>. The alpha helices are located on the outside while the beta sheets are found more toward the center. The NMDA receptor has polar amino acid side-chains located extracellularly and at the ion-pore, but also many non-polar side chains at points where the protein passes through the phospholipid bilayer.
+To date, the entire X-ray or NMR crystal structure of the <scene name='Sandbox42/Initial/1'>NMDA receptor</scene> has not been produced. However, there are many structural subunits of NMDA that have successfully been crystallized and analyzed which provide some structural information about the NMDA receptor. The architecture of NMDA receptors is modular and is composed of multiple domains with distinct functional roles. The large extracellular region of the receptor is partitioned into two domains: an <scene name='Sandbox42/Atd/1'>amino-terminal domain</scene> (ATD) and a <scene name='Sandbox42/Lbd/2'>ligand-binding domain</scene> (LBD) (7). Each domain consists of 8 <scene name='Sandbox42/Alpha/2'>alpha helices</scene> and antiparallel <scene name='Sandbox42/Beta/4'>beta sheets</scene>. The alpha helices are located on the outside while the beta sheets are found more toward the center. The NMDA receptor has polar amino acid side-chains located extracellularly and at the ion-pore, but also many non-polar side chains at points where the protein passes through the phospholipid bilayer.
-The ligand-binding domain of NMDA receptors are heterotetrameric ion channels composed of two copies of the glycine-binding NR1 subunit and two copies of the L-glutamate-binding NR2 subunit. The NR1 subunit is further divided up into splice units while the NR2 subunit has four sub-variants (NR2A-NR2D). The receptor as a whole has four general ligand binding sites (7).
+The ligand-binding domain of NMDA receptors are heterotetrameric ion channels composed of two copies of the glycine-binding NR1 subunit and two copies of the L-glutamate-binding NR2 subunit. The NR1 subunit is further divided up into splice units while the NR2 subunit has four sub-variants (NR2A-NR2D). The receptor as a whole has four general ligand binding sites (8).
-The amino-terminal domain has an overall clamshell shaped structure and is notably distinct from non-NMDA receptor ATD's. The most important ATD is the NR2B ATD and it is particularly important in current research. It has been shown that the binding of Zn2+ provides neuroprotective agents without the adverse side effects that are more commonly observed with LBD agonists. NR2B ATD has the typical clamshell-like architecture composed of two domains, R1 and R2, which are tied together by three well-structured loops. There is a distinct R1–R2 domain orientation, which in NR2B ATD, is ‘twisted’ by a striking rotation of B45 and 541 compared with the R1–R2 orientation in GluR2 ATD or GluR6 ATD (6).
+The amino-terminal domain has an overall clamshell shaped structure and is notably distinct from non-NMDA receptor ATD's. The most important ATD is the NR2B ATD and it is particularly important in current research. It has been shown that the binding of Zn2+ provides neuroprotective agents without the adverse side effects that are more commonly observed with LBD agonists. NR2B ATD has the typical clamshell-like architecture composed of two domains, R1 and R2, which are tied together by three well-structured loops. There is a distinct R1–R2 domain orientation, which in NR2B ATD, is ‘twisted’ by a striking rotation of B45 and 541 compared with the R1–R2 orientation in GluR2 ATD or GluR6 ATD (7).
-There are three types of sub units of an NMDA receptor, but not all receptors have the same composition of subtypes. Each subunit consists of  three transmembrane segments, a P loop, and an intracellular C-terminus domain (CTD). The segments S1 and S2 in the LBD form a venus-flytrap structure and define the region for agonist recognition (7).
+There are three types of sub units of an NMDA receptor, but not all receptors have the same composition of subtypes. Each subunit consists of  three transmembrane segments, a P loop, and an intracellular C-terminus domain (CTD). The segments S1 and S2 in the LBD form a venus-flytrap structure and define the region for agonist recognition (8).
 The first molecule is the closed NMDA receptor in its natural state. The second is the open NMDA receptor when it is bound by glutamate and co-agonist glycine. The third is the closed form of the NR2B subunit when it is bound by Zn2+. The fourth is the open state of the NR2B subunit.