Sandbox Reserved 1649: Difference between revisions
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'''Transmembrane domain''' | '''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. Structurally, there is a small loop of 150 amino acids between M3 and M4. <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 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> | M2 loop is a channel-lining loop and located in transmembrane domain. Two 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> | ||
Ethanol acts as an inhibitor on NMDAr. 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> | Ethanol acts as an inhibitor on NMDAr. 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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</ref> | </ref> | ||
NMDA receptors are inhibited by ethanol. Mutagenesis of an F residue in the transmembrane domain has made it possible to characterize the role of the latter in this inhibition | NMDA receptors are inhibited by ethanol. Mutagenesis of an F residue in the transmembrane domain has made it possible to characterize the role of the latter in this inhibition. On the other hand, the phenylalanine residue at position 639 is replaced by an alanine in the transmembrane domain (in part M3) and the results show significantly less inhibition by ethanol of NMDA compared to wild type receptors.<ref name="ethanol inhibition">DOI 10.1074 / jbc.M102800200</ref> | ||
== Disease == | == Disease == | ||
