What is the structure of the NMDA receptor?
Best insight from top research papers
The NMDA receptor is a tetrameric complex composed of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits . These subunits can assemble in various combinations, resulting in different receptor subtypes with distinct functional and pharmacological properties . The receptor structure consists of transmembrane domains and extracellular domains, which undergo conformational changes upon ligand binding . The ligand-binding domains are responsible for the energy of fast channel opening, while the pre-M1 helix and S2-M4 segments play a role in removing constraints and priming the channel for rapid opening . The NMDA receptor gating is complex, with multiple closed, open, and desensitized states, and the energy landscape of the transmembrane domains is influenced by liganded conditions . Overall, the structure of the NMDA receptor is crucial for its function in mediating excitatory neurotransmission and synaptic plasticity in the central nervous system .
Answers from top 5 papers
More filters
| Papers (5) | Insight |
|---|---|
41 Citations | The structure of the NMDA receptor is complex, exhibiting multiple closed, open, and desensitized states. |
| The structure of the NMDA receptor includes the ligand-binding domains, the pore-forming M3 segments, and the pre-M1 helix and S2-M4 structures. | |
| The structure of the NMDA receptor is complex and consists of multiple subunits that form tetrameric receptor complexes. | |
31 Citations | The NMDA receptor is a tetrameric complex consisting of two GluN1 subunits and two GluN2 subunits. |
| The structure of the NMDA receptor is not mentioned in the provided information. |
Related Questions
What are the specific molecular mechanisms by which NMDA receptor structure contributes to the pathophysiology of bipolar disorder?4 answersThe NMDA receptor (NMDAR) structure plays a crucial role in the pathophysiology of bipolar disorder (BD) through several molecular mechanisms. Genetic studies have identified associations between BD and genes encoding NMDAR subunits, suggesting a genetic predisposition that affects NMDAR function in BD patients. Specifically, variations in genes encoding the NMDA 1, 2A, and 2B subunits have been implicated, pointing towards a potential decrease in the density of NMDAR and a reduction in NMDA-mediated glutamatergic activity in individuals with BD. This is further supported by findings that suggest a reduced activity of NMDARs in key brain regions such as the prefrontal and superior temporal cortex, anterior cingulate cortex, and hippocampus.
Moreover, the structure of NMDARs, which are heterotetrameric complexes composed of two GluN1 and two GluN2B subunits, plays a significant role in their function. The arrangement of these subunits around the central pore and the layered receptor domains, including the amino terminal domain (ATD), the transmembrane domain (TMD), and the ligand-binding domain (LBD), are crucial for NMDAR's role in synaptic plasticity and learning. Dysregulation of NMDAR signaling, as evidenced by decreased DAO protein abundance and enzymatic activity in a knock-in mouse model, has been linked to enhanced stress susceptibility and altered behavioral responses, which are characteristic of BD.
Furthermore, the pre-M1 region of the NMDAR, particularly the GluN2 pre-M1 helix and linker between the ABD and M1, has been identified as crucial for gating and synaptic function. Mutations in this region can lead to prolonged glutamate response time courses and increased charge transfer during synaptic-like activation, promoting excitotoxic damage and contributing to the pathophysiology of BD. This suggests that the structural components of NMDARs are directly involved in the molecular mechanisms underlying BD, influencing glutamatergic transmission, synaptic plasticity, and neuronal health.
What is the role of NMDA in cortical reorganization?5 answersNMDA receptors play a crucial role in cortical reorganization by mediating various processes such as dendritic remodeling, neuronal morphology alterations, and synaptic reorganization. Activation of NMDA receptors is linked to stress-induced dendritic atrophy in the prefrontal cortex, highlighting their involvement in structural changes due to stress. In the context of acquired brain malformations and epilepsy, severe seizure activity triggers a progressive architectural, neuronal, and synaptic reorganization in the brain, with NMDA hyper-activation being mechanistically relevant in this pathologic plasticity. Furthermore, disruption of NMDA receptor function can lead to significant disturbances in visual map alignment in the superior colliculus, emphasizing the critical role of NMDA receptors in activity-dependent processes that shape cortical connectivity.
What is the structure of GABA A receptors?3 answersGABA A receptors are pentameric ligand-gated ion channels that play a crucial role in neuronal inhibition in the brain. They are composed of a combination of 19 different subunits, resulting in a wide variety of receptor isoforms with distinct pharmacological and physiological properties. The most common assembly of GABA A receptors consists of two α subunits, two β subunits, and one γ subunit arranged counterclockwise around the center. Recent structural studies using cryo-electron microscopy have provided insights into the organization of GABA A receptors. These studies have revealed that GABA A receptors have a central chloride ion channel gated by GABA neurotransmitter and modulated by various drugs. The structures also show that GABA A receptors can interact with different drugs, such as benzodiazepines and general anesthetics, providing a basis for the development of subunit-specific modulators. Overall, the structure of GABA A receptors is complex and diverse, with multiple subunit assemblies and binding sites for various ligands.
Past decade updates on NMDA receptor therapeutic for brain injury?5 answersOver the past decade, research on NMDA receptor therapeutics for brain injury has shown mixed results. Initial studies suggested that NMDA receptor antagonists could improve recovery after traumatic brain injury (TBI) and stroke. However, large-scale clinical trials have failed to demonstrate any benefit or have even shown deleterious effects. This has led to a shift in focus towards understanding the dynamic changes of NMDA receptors after brain insult. It has been found that early hyperactivation of NMDA receptors is followed by a loss of functional receptors that persists for weeks. As a result, alternative treatment approaches, such as activation rather than blockade of NMDA receptors, have been proposed. One such approach is the use of the partial agonist Dcycloserine (DCS), which has shown promising results in improving recovery and cognitive function in animal models of TBI and stroke. DCS has also shown benefits in other animal models and clinical indications involving disruptions in NMDA receptor function. Based on these findings, a clinical trial assessing the effect of DCS on cognitive outcome in patients with moderate TBI has recently begun.
Which pharmacological agents target the NMDA receptor for brain injury?5 answersNMDA receptor is targeted by several pharmacological agents for brain injury. Traxoprodil (CP-101,606) is a selective NR2B subunit antagonist that has shown neuroprotective effects in animal models of brain injury and ischemia. SP-8203, derived from earthworm extracts, has been found to block NMDA receptor-mediated excitotoxicity and has shown neuroprotective effects in cerebral ischemia. Other NMDA receptor antagonists such as Selfotel, Aptiganel, and Gavestinel have been tested in clinical trials but have not shown neuroprotective efficacy or have produced adverse effects. The use of NMDA receptor antagonists in stroke and traumatic brain injury is an area of ongoing research and clinical trials.
Are NMDA receptors Metabotropic?5 answers