1nnp: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1nnp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NNP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NNP FirstGlance]. <br>
<table><tr><td colspan='2'>[[1nnp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NNP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NNP FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CE2:3-(5-TERT-BUTYL-3-OXIDOISOXAZOL-4-YL)-L-ALANINATE'>CE2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CE2:3-(5-TERT-BUTYL-3-OXIDOISOXAZOL-4-YL)-L-ALANINATE'>CE2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ftj|1ftj]], [[1ftk|1ftk]], [[1fto|1fto]], [[1fw0|1fw0]], [[1ftm|1ftm]], [[1ftl|1ftl]], [[1gr2|1gr2]], [[1lb8|1lb8]], [[1lb9|1lb9]], [[1lbc|1lbc]], [[1m5e|1m5e]], [[1m5c|1m5c]], [[1m5d|1m5d]], [[1m5b|1m5b]], [[1m5f|1m5f]], [[1mm7|1mm7]], [[1mm6|1mm6]], [[1lbb|1lbb]], [[1my4|1my4]], [[1my3|1my3]], [[1nnk|1nnk]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ftj|1ftj]], [[1ftk|1ftk]], [[1fto|1fto]], [[1fw0|1fw0]], [[1ftm|1ftm]], [[1ftl|1ftl]], [[1gr2|1gr2]], [[1lb8|1lb8]], [[1lb9|1lb9]], [[1lbc|1lbc]], [[1m5e|1m5e]], [[1m5c|1m5c]], [[1m5d|1m5d]], [[1m5b|1m5b]], [[1m5f|1m5f]], [[1mm7|1mm7]], [[1mm6|1mm6]], [[1lbb|1lbb]], [[1my4|1my4]], [[1my3|1my3]], [[1nnk|1nnk]]</td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nnp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nnp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1nnp RCSB], [http://www.ebi.ac.uk/pdbsum/1nnp PDBsum]</span></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=1nnp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nnp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1nnp RCSB], [http://www.ebi.ac.uk/pdbsum/1nnp PDBsum]</span></td></tr>
<table>
</table>
== Function ==
[[http://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> 
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</StructureSection>
</StructureSection>
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Egebjerg, J.]]
[[Category: Egebjerg, J]]
[[Category: Gouaux, E.]]
[[Category: Gouaux, E]]
[[Category: Hogner, A.]]
[[Category: Hogner, A]]
[[Category: Kastrup, J S.]]
[[Category: Kastrup, J S]]
[[Category: Lunn, M L.]]
[[Category: Lunn, M L]]
[[Category: Stensbol, T B.]]
[[Category: Stensbol, T B]]
[[Category: Agonist complex.]]
[[Category: Agonist complex]]
[[Category: Ionotropic glutamate receptor glur2]]
[[Category: Ionotropic glutamate receptor glur2]]
[[Category: Ligand-binding core]]
[[Category: Ligand-binding core]]
[[Category: Membrane protein]]
[[Category: Membrane protein]]

Revision as of 13:58, 25 December 2014

X-ray structure of the GluR2 ligand-binding core (S1S2J) in complex with (S)-ATPA at 1.9 A resolution. Crystallization without zinc ions.X-ray structure of the GluR2 ligand-binding core (S1S2J) in complex with (S)-ATPA at 1.9 A resolution. Crystallization without zinc ions.

Structural highlights

1nnp is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Resources:FirstGlance, OCA, RCSB, PDBsum

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Two X-ray structures of the GluR2 ligand-binding core in complex with (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid ((S)-ATPA) have been determined with and without Zn(2+) ions. (S)-ATPA induces a domain closure of ca. 21 degrees compared to the apo form. The tert-butyl moiety of (S)-ATPA is buried in a partially hydrophobic pocket and forces the ligand into the glutamate-like binding mode. The structures provide new insight into the molecular basis of agonist selectivity between AMPA and kainate receptors.

Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA: implications for receptor subunit selectivity.,Lunn ML, Hogner A, Stensbol TB, Gouaux E, Egebjerg J, Kastrup JS J Med Chem. 2003 Feb 27;46(5):872-5. PMID:12593667[15]

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

See Also

References

  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:http://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. ↑ Lunn ML, Hogner A, Stensbol TB, Gouaux E, Egebjerg J, Kastrup JS. Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA: implications for receptor subunit selectivity. J Med Chem. 2003 Feb 27;46(5):872-5. PMID:12593667 doi:10.1021/jm021020+

1nnp, resolution 1.90Å

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