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4u1y

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Revision as of 09:19, 22 November 2017

Full length GluA2-FW-(R,R)-2b complex

Structural highlights

4u1y is a 4 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	Gria2, Glur2 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14]

Publication Abstract from PubMed

Ionotropic glutamate receptors (iGluRs) mediate the majority of fast excitatory signaling in the nervous system. Despite the profound importance of iGluRs to neurotransmission, little is known about the structures and dynamics of intact receptors in distinct functional states. Here, we elucidate the structures of the intact GluA2 AMPA receptor in an apo resting/closed state, in an activated/pre-open state bound with partial agonists and a positive allosteric modulator, and in a desensitized/closed state in complex with fluorowilliardiine. To probe the conformational properties of these states, we carried out double electron-electron resonance experiments on cysteine mutants and cryoelectron microscopy studies. We show how agonist binding modulates the conformation of the ligand-binding domain "layer" of the intact receptors and how, upon desensitization, the receptor undergoes large conformational rearrangements of the amino-terminal and ligand-binding domains. We define mechanistic principles by which to understand antagonism, activation, and desensitization in AMPA iGluRs.

Structure and Dynamics of AMPA Receptor GluA2 in Resting, Pre-Open, and Desensitized States.,Durr KL, Chen L, Stein RA, De Zorzi R, Folea IM, Walz T, Mchaourab HS, Gouaux E Cell. 2014 Aug 14;158(4):778-92. doi: 10.1016/j.cell.2014.07.023. Epub 2014 Aug, 7. PMID:25109876^[15]

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

References

↑ Everts I, Villmann C, Hollmann M. N-Glycosylation is not a prerequisite for glutamate receptor function but Is essential for lectin modulation. Mol Pharmacol. 1997 Nov;52(5):861-73. PMID:9351977
↑ 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
↑ Kato AS, Gill MB, Ho MT, Yu H, Tu Y, Siuda ER, Wang H, Qian YW, Nisenbaum ES, Tomita S, Bredt DS. Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins. Neuron. 2010 Dec 22;68(6):1082-96. doi: 10.1016/j.neuron.2010.11.026. PMID:21172611 doi:10.1016/j.neuron.2010.11.026
↑ Jin R, Horning M, Mayer ML, Gouaux E. Mechanism of activation and selectivity in a ligand-gated ion channel: structural and functional studies of GluR2 and quisqualate. Biochemistry. 2002 Dec 31;41(52):15635-43. PMID:12501192
↑ Sun Y, Olson R, Horning M, Armstrong N, Mayer M, Gouaux E. Mechanism of glutamate receptor desensitization. Nature. 2002 May 16;417(6886):245-53. PMID:12015593 doi:10.1038/417245a
↑ Jin R, Banke TG, Mayer ML, Traynelis SF, Gouaux E. Structural basis for partial agonist action at ionotropic glutamate receptors. Nat Neurosci. 2003 Aug;6(8):803-10. PMID:12872125 doi:10.1038/nn1091
↑ Armstrong N, Mayer M, Gouaux E. Tuning activation of the AMPA-sensitive GluR2 ion channel by genetic adjustment of agonist-induced conformational changes. Proc Natl Acad Sci U S A. 2003 May 13;100(10):5736-41. Epub 2003 May 2. PMID:12730367 doi:http://dx.doi.org/10.1073/pnas.1037393100
↑ Jin R, Clark S, Weeks AM, Dudman JT, Gouaux E, Partin KM. Mechanism of positive allosteric modulators acting on AMPA receptors. J Neurosci. 2005 Sep 28;25(39):9027-36. PMID:16192394 doi:25/39/9027
↑ Frandsen A, Pickering DS, Vestergaard B, Kasper C, Nielsen BB, Greenwood JR, Campiani G, Fattorusso C, Gajhede M, Schousboe A, Kastrup JS. Tyr702 is an important determinant of agonist binding and domain closure of the ligand-binding core of GluR2. Mol Pharmacol. 2005 Mar;67(3):703-13. Epub 2004 Dec 9. PMID:15591246 doi:10.1124/mol.104.002931
↑ Armstrong N, Jasti J, Beich-Frandsen M, Gouaux E. Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor. Cell. 2006 Oct 6;127(1):85-97. PMID:17018279 doi:10.1016/j.cell.2006.08.037
↑ Kasper C, Pickering DS, Mirza O, Olsen L, Kristensen AS, Greenwood JR, Liljefors T, Schousboe A, Watjen F, Gajhede M, Sigurskjold BW, Kastrup JS. The structure of a mixed GluR2 ligand-binding core dimer in complex with (S)-glutamate and the antagonist (S)-NS1209. J Mol Biol. 2006 Apr 7;357(4):1184-201. Epub 2006 Jan 31. PMID:16483599 doi:10.1016/j.jmb.2006.01.024
↑ Sobolevsky AI, Rosconi MP, Gouaux E. X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature. 2009 Dec 10;462(7274):745-56. Epub . PMID:19946266 doi:10.1038/nature08624
↑ Rossmann M, Sukumaran M, Penn AC, Veprintsev DB, Babu MM, Greger IH. Subunit-selective N-terminal domain associations organize the formation of AMPA receptor heteromers. EMBO J. 2011 Mar 2;30(5):959-71. Epub 2011 Feb 11. PMID:21317873 doi:10.1038/emboj.2011.16
↑ Ahmed AH, Wang S, Chuang HH, Oswald RE. Mechanism of AMPA receptor activation by partial agonists: disulfide trapping of closed lobe conformations. J Biol Chem. 2011 Aug 16. PMID:21846932 doi:10.1074/jbc.M111.269001
↑ Durr KL, Chen L, Stein RA, De Zorzi R, Folea IM, Walz T, Mchaourab HS, Gouaux E. Structure and Dynamics of AMPA Receptor GluA2 in Resting, Pre-Open, and Desensitized States. Cell. 2014 Aug 14;158(4):778-92. doi: 10.1016/j.cell.2014.07.023. Epub 2014 Aug, 7. PMID:25109876 doi:http://dx.doi.org/10.1016/j.cell.2014.07.023

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4u1y"

@@ Line 3: / Line 3: @@
 <StructureSection load='4u1y' size='340' side='right' caption='[[4u1y]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4u1y]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U1Y FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4u1y]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U1Y FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FWD:2-AMINO-3-(5-FLUORO-2,4-DIOXO-3,4-DIHYDRO-2H-PYRIMIDIN-1-YL)-PROPIONIC+ACID'>FWD</scene>, <scene name='pdbligand=FWF:N,N-[BIPHENYL-4,4-DIYLDI(2R)PROPANE-2,1-DIYL]DIPROPANE-2-SULFONAMIDE'>FWF</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u1y OCA], [http://pdbe.org/4u1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u1y RCSB], [http://www.ebi.ac.uk/pdbsum/4u1y PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gria2, Glur2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u1y OCA], [http://pdbe.org/4u1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u1y RCSB], [http://www.ebi.ac.uk/pdbsum/4u1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u1y ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 4u1y" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
 [[Category: Chen, L]]
 [[Category: Gouaux, E]]

4u1y

From Proteopedia

Revision as of 09:19, 22 November 2017

Full length GluA2-FW-(R,R)-2b complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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