|
|
| Line 3: |
Line 3: |
| | <SX load='5up2' size='340' side='right' viewer='molstar' caption='[[5up2]], [[Resolution|resolution]] 6.00Å' scene=''> | | <SX load='5up2' size='340' side='right' viewer='molstar' caption='[[5up2]], [[Resolution|resolution]] 6.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5up2]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UP2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UP2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5up2]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UP2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uow|5uow]]</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5up2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5up2 OCA], [https://pdbe.org/5up2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5up2 RCSB], [https://www.ebi.ac.uk/pdbsum/5up2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5up2 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LOC100127346 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog]), NR2B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5up2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5up2 OCA], [http://pdbe.org/5up2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5up2 RCSB], [http://www.ebi.ac.uk/pdbsum/5up2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5up2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/NMDE2_XENLA NMDE2_XENLA] Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:18177891, PubMed:25008524, PubMed:28232581). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable).<ref>PMID:18177891</ref> <ref>PMID:25008524</ref> <ref>PMID:28232581</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 26: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: African clawed frog]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Du, J]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Goehring, A]] | + | [[Category: Du J]] |
| - | [[Category: Gouaux, E]] | + | [[Category: Goehring A]] |
| - | [[Category: Lu, W]] | + | [[Category: Gouaux E]] |
| - | [[Category: Membrane protein]]
| + | [[Category: Lu W]] |
| Structural highlights
Function
NMDE2_XENLA Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:18177891, PubMed:25008524, PubMed:28232581). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable).[1] [2] [3]
Publication Abstract from PubMed
N-methyl-D-aspartate receptors (NMDARs) are heterotetrameric ion channels assembled as diheteromeric or triheteromeric complexes. Here, we report structures of the triheteromeric GluN1/GluN2A/GluN2B receptor in the absence or presence of the GluN2B-specific allosteric modulator Ro 25-6981 (Ro), determined by cryogenic electron microscopy (cryo-EM). In the absence of Ro, the GluN2A and GluN2B amino terminal domains (ATD) adopt "closed" and "open" clefts, respectively. Upon binding Ro, the GluN2B ATD clamshell transitions from an open to a closed conformation. Consistent with a predominance of the GluN2A subunit in ion channel gating, the GluN2A subunit interacts more extensively with GluN1 subunits throughout the receptor, in comparison with the GluN2B subunit. Differences in the conformation of the pseudo 2-fold related GluN1 subunits further reflect receptor asymmetry. The triheteromeric NMDAR structures provide the first view of the most common NMDA receptor assembly and show how incorporation of two different GluN2 subunits modifies receptor symmetry and subunit interactions, allowing each subunit to uniquely influence receptor structure and function, thus increasing receptor complexity.
Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation.,Lu W, Du J, Goehring A, Gouaux E Science. 2017 Feb 23. pii: eaal3729. doi: 10.1126/science.aal3729. PMID:28232581[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schmidt C, Hollmann M. Apparent homomeric NR1 currents observed in Xenopus oocytes are caused by an endogenous NR2 subunit. J Mol Biol. 2008 Feb 22;376(3):658-70. PMID:18177891 doi:10.1016/j.jmb.2007.11.105
- ↑ Lee CH, Lu W, Michel JC, Goehring A, Du J, Song X, Gouaux E. NMDA receptor structures reveal subunit arrangement and pore architecture. Nature. 2014 Jul 10;511(7508):191-7. doi: 10.1038/nature13548. Epub 2014 Jun 22. PMID:25008524 doi:http://dx.doi.org/10.1038/nature13548
- ↑ Lu W, Du J, Goehring A, Gouaux E. Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation. Science. 2017 Feb 23. pii: eaal3729. doi: 10.1126/science.aal3729. PMID:28232581 doi:http://dx.doi.org/10.1126/science.aal3729
- ↑ Lu W, Du J, Goehring A, Gouaux E. Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation. Science. 2017 Feb 23. pii: eaal3729. doi: 10.1126/science.aal3729. PMID:28232581 doi:http://dx.doi.org/10.1126/science.aal3729
|
