6njn: Difference between revisions

Latest revision as of 09:56, 25 December 2024

Architecture and subunit arrangement of native AMPA receptors

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Structural highlights

6njn is a 15 chain structure with sequence from Mus musculus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 6.5Å
Ligands:	BMA, NAG, ZK1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GRIA1_RAT Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.^[1] ^[2]

Publication Abstract from PubMed

Glutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric assemblies composed of four subunits, GluA1-4. Despite decades of study, the subunit composition, subunit arrangement and molecular structure of native AMPA receptors remain unknown. Here we elucidate the structures of 10 distinct native AMPA receptor complexes by single particle cryo-EM. We find that receptor subunits are arranged non stochastically, with the GluA2 subunit preferentially occupying the B and D positions of the tetramer and with triheteromeric assemblies comprising a major population of native AMPA receptors. Cryo-EM maps define the structure for S2-M4 linkers between the ligand binding and transmembrane domains, suggesting how neurotransmitter binding is coupled to ion channel gating.

Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM.,Zhao Y, Chen S, Swensen AC, Qian WJ, Gouaux E Science. 2019 Apr 11. pii: science.aaw8250. doi: 10.1126/science.aaw8250. PMID:30975770^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bedoukian MA, Weeks AM, Partin KM. Different domains of the AMPA receptor direct stargazin-mediated trafficking and stargazin-mediated modulation of kinetics. J Biol Chem. 2006 Aug 18;281(33):23908-21. Epub 2006 Jun 22. PMID:16793768 doi:https://dx.doi.org/M600679200
↑ Schwenk J, Harmel N, Zolles G, Bildl W, Kulik A, Heimrich B, Chisaka O, Jonas P, Schulte U, Fakler B, Klocker N. Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors. Science. 2009 Mar 6;323(5919):1313-9. doi: 10.1126/science.1167852. PMID:19265014 doi:10.1126/science.1167852
↑ Zhao Y, Chen S, Swensen AC, Qian WJ, Gouaux E. Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM. Science. 2019 Apr 11. pii: science.aaw8250. doi: 10.1126/science.aaw8250. PMID:30975770 doi:https://dx.doi.org/10.1126/science.aaw8250

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OCA

[1] Bedoukian MA, Weeks AM, Partin KM. Different domains of the AMPA receptor direct stargazin-mediated trafficking and stargazin-mediated modulation of kinetics. J Biol Chem. 2006 Aug 18;281(33):23908-21. Epub 2006 Jun 22. PMID:16793768 doi:https://dx.doi.org/M600679200

[2] Schwenk J, Harmel N, Zolles G, Bildl W, Kulik A, Heimrich B, Chisaka O, Jonas P, Schulte U, Fakler B, Klocker N. Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors. Science. 2009 Mar 6;323(5919):1313-9. doi: 10.1126/science.1167852. PMID:19265014 doi:10.1126/science.1167852

[3] Zhao Y, Chen S, Swensen AC, Qian WJ, Gouaux E. Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM. Science. 2019 Apr 11. pii: science.aaw8250. doi: 10.1126/science.aaw8250. PMID:30975770 doi:https://dx.doi.org/10.1126/science.aaw8250

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[2]

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@@ Line 3: / Line 3: @@
 <SX load='6njn' size='340' side='right' viewer='molstar' caption='[[6njn]], [[Resolution|resolution]] 6.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6njn]] is a 15 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NJN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6njn]] is a 15 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NJN FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZK1:{[7-MORPHOLIN-4-YL-2,3-DIOXO-6-(TRIFLUOROMETHYL)-3,4-DIHYDROQUINOXALIN-1(2H)-YL]METHYL}PHOSPHONIC+ACID'>ZK1</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]] 6.5&#8491;</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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZK1:{[7-MORPHOLIN-4-YL-2,3-DIOXO-6-(TRIFLUOROMETHYL)-3,4-DIHYDROQUINOXALIN-1(2H)-YL]METHYL}PHOSPHONIC+ACID'>ZK1</scene></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=6njn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6njn OCA], [https://pdbe.org/6njn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6njn RCSB], [https://www.ebi.ac.uk/pdbsum/6njn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6njn ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/GRIA3_RAT GRIA3_RAT]] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate (By similarity). [[https://www.uniprot.org/uniprot/GRIA2_RAT GRIA2_RAT]] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:9351977</ref> <ref>PMID:19265014</ref> <ref>PMID:21172611</ref> <ref>PMID:12501192</ref> <ref>PMID:12015593</ref> <ref>PMID:12872125</ref> <ref>PMID:12730367</ref> <ref>PMID:16192394</ref> <ref>PMID:15591246</ref> <ref>PMID:17018279</ref> <ref>PMID:16483599</ref> <ref>PMID:19946266</ref> <ref>PMID:21317873</ref> <ref>PMID:21846932</ref>  [[https://www.uniprot.org/uniprot/GRIA1_RAT GRIA1_RAT]] Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:16793768</ref> <ref>PMID:19265014</ref>  [[https://www.uniprot.org/uniprot/CCG2_RAT CCG2_RAT]] Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.<ref>PMID:17880894</ref> <ref>PMID:18817736</ref> <ref>PMID:19234459</ref> <ref>PMID:19265014</ref> <ref>PMID:20805473</ref>
+[https://www.uniprot.org/uniprot/GRIA1_RAT GRIA1_RAT] Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:16793768</ref> <ref>PMID:19265014</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 *[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
 *[[Ion channels 3D structures|Ion channels 3D structures]]
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 == References ==
 <references/>
@@ Line 28: / Line 29: @@
 </SX>
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
 [[Category: Rattus norvegicus]]
-[[Category: Gouaux, E]]
+[[Category: Gouaux E]]
-[[Category: Zhao, Y]]
+[[Category: Zhao Y]]
-[[Category: Ampa receptor]]
-[[Category: Ligand gated ion channel]]
-[[Category: Membrane protein]]
-[[Category: Neurotransmitter]]
-[[Category: Synapse]]

6njn: Difference between revisions

Latest revision as of 09:56, 25 December 2024

Architecture and subunit arrangement of native AMPA receptors

Structural highlights

Function

Publication Abstract from PubMed

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References

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