5kbv: Difference between revisions

Revision as of 12:10, 25 December 2019

Cryo-EM structure of GluA2 bound to antagonist ZK200775 at 6.8 Angstrom resolution

Structural highlights

5kbv 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:	NAG, ZK1
Related:	5kbs, 5kbu, 5kbt
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

AMPA-subtype ionotropic glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and contribute to high cognitive processes such as learning and memory. In the brain, AMPAR trafficking, gating, and pharmacology is tightly controlled by transmembrane AMPAR regulatory proteins (TARPs). Here, we used cryo-electron microscopy to elucidate the structural basis of AMPAR regulation by one of these auxiliary proteins, TARP gamma2, or stargazin (STZ). Our structures illuminate the variable interaction stoichiometry of the AMPAR-TARP complex, with one or two TARP molecules binding one tetrameric AMPAR. Analysis of the AMPAR-STZ binding interfaces suggests that electrostatic interactions between the extracellular domains of AMPAR and STZ play an important role in modulating AMPAR function through contact surfaces that are conserved across AMPARs and TARPs. We propose a model explaining how TARPs stabilize the activated state of AMPARs and how the interactions between AMPARs and their auxiliary proteins control fast excitatory synaptic transmission.

Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy.,Twomey EC, Yelshanskaya MV, Grassucci RA, Frank J, Sobolevsky AI Science. 2016 Jul 1;353(6294):83-6. doi: 10.1126/science.aaf8411. PMID:27365450^[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:https://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
↑ Twomey EC, Yelshanskaya MV, Grassucci RA, Frank J, Sobolevsky AI. Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy. Science. 2016 Jul 1;353(6294):83-6. doi: 10.1126/science.aaf8411. PMID:27365450 doi:https://dx.doi.org/10.1126/science.aaf8411

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[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] 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

[4] 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

[5] 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

[6] 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

[7] 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:https://dx.doi.org/10.1073/pnas.1037393100

[8] 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

[9] 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

[10] 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

[11] 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

[12] 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

[13] 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

[14] 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

[15] Twomey EC, Yelshanskaya MV, Grassucci RA, Frank J, Sobolevsky AI. Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy. Science. 2016 Jul 1;353(6294):83-6. doi: 10.1126/science.aaf8411. PMID:27365450 doi:https://dx.doi.org/10.1126/science.aaf8411

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@@ Line 1: / Line 1: @@
 ==Cryo-EM structure of GluA2 bound to antagonist ZK200775 at 6.8 Angstrom resolution==
-<StructureSection load='5kbv' size='340' side='right' caption='[[5kbv]], [[Resolution|resolution]] 6.80&Aring;' scene=''>
+<StructureSection load='5kbv' size='340' side='right'caption='[[5kbv]], [[Resolution|resolution]] 6.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5kbv]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KBV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5kbv]] 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=5KBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KBV FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kbs|5kbs]], [[5kbu|5kbu]], [[5kbt|5kbt]]</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=5kbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kbv OCA], [http://pdbe.org/5kbv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kbv RCSB], [http://www.ebi.ac.uk/pdbsum/5kbv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kbv ProSAT]</span></td></tr>
 </table>
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5kbv" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
+[[Category: Large Structures]]
 [[Category: Frank, J]]
 [[Category: Grassucci, R G]]

5kbv: Difference between revisions

Revision as of 12:10, 25 December 2019

Cryo-EM structure of GluA2 bound to antagonist ZK200775 at 6.8 Angstrom resolution

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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