5kk2: Difference between revisions

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<StructureSection load='5kk2' size='340' side='right' caption='[[5kk2]], [[Resolution|resolution]] 7.30&Aring;' scene=''>
<StructureSection load='5kk2' size='340' side='right' caption='[[5kk2]], [[Resolution|resolution]] 7.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5kk2]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KK2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KK2 FirstGlance]. <br>
<table><tr><td colspan='2'>[[5kk2]] is a 8 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=5KK2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KK2 FirstGlance]. <br>
</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=5kk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kk2 OCA], [http://pdbe.org/5kk2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kk2 RCSB], [http://www.ebi.ac.uk/pdbsum/5kk2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kk2 ProSAT]</span></td></tr>
</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]), Cacng2 ([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=5kk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kk2 OCA], [http://pdbe.org/5kk2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kk2 RCSB], [http://www.ebi.ac.uk/pdbsum/5kk2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kk2 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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</div>
</div>
<div class="pdbe-citations 5kk2" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 5kk2" style="background-color:#fffaf0;"></div>
==See Also==
*[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Buffalo rat]]
[[Category: Baconguis, I]]
[[Category: Baconguis, I]]
[[Category: Chen, S]]
[[Category: Chen, S]]

Revision as of 11:50, 18 July 2018

Architecture of fully occupied GluA2 AMPA receptor - TARP complex elucidated by single particle cryo-electron microscopyArchitecture of fully occupied GluA2 AMPA receptor - TARP complex elucidated by single particle cryo-electron microscopy

Structural highlights

5kk2 is a 8 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:Gria2, Glur2 (Buffalo rat), Cacng2 (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] [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.[15] [16] [17] [18] [19]

Publication Abstract from PubMed

Fast excitatory neurotransmission in the mammalian central nervous system is largely carried out by AMPA-sensitive ionotropic glutamate receptors1. Localized within the postsynaptic density of glutamatergic spines, AMPA receptors are composed of heterotetrameric receptor assemblies associated with auxiliary subunits, the most common of which are transmembrane AMPA-receptor regulatory proteins (TARPs). The association of TARPs with AMPA receptors modulates the kinetics of receptor gating and pharmacology, as well as trafficking2. Here we report the cryo-EM structure of the homomeric GluA2 AMPA receptor saturated with TARP gamma2 subunits, showing how the TARPs are arranged with four-fold symmetry around the ion channel domain, making extensive interactions with the M1, M2 and M4 TM helices. Poised like partially opened 'hands' underneath the two-fold symmetric ligand binding domain (LBD) 'clamshells', one pair of TARPs are juxtaposed near the LBD dimer interface, while the other pair are near the LBD dimer-dimer interface. The extracellular 'domains' of TARP are positioned to not only modulate LBD 'clamshell' closure, but also affect conformational rearrangements of the LBD layer associated with receptor activation and desensitization, while the TARP transmembrane (TM) domains buttress the ion channel pore.

Architecture of fully occupied GluA2 AMPA receptor-TARP complex elucidated by cryo-EM.,Zhao Y, Chen S, Yoshioka C, Baconguis I, Gouaux E Nature. 2016 Jul 1. doi: 10.1038/nature18961. PMID:27368053[20]

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. ↑ Milstein AD, Zhou W, Karimzadegan S, Bredt DS, Nicoll RA. TARP subtypes differentially and dose-dependently control synaptic AMPA receptor gating. Neuron. 2007 Sep 20;55(6):905-18. PMID:17880894 doi:http://dx.doi.org/10.1016/j.neuron.2007.08.022
  16. ↑ Kato AS, Siuda ER, Nisenbaum ES, Bredt DS. AMPA receptor subunit-specific regulation by a distinct family of type II TARPs. Neuron. 2008 Sep 25;59(6):986-96. doi: 10.1016/j.neuron.2008.07.034. PMID:18817736 doi:http://dx.doi.org/10.1016/j.neuron.2008.07.034
  17. ↑ Soto D, Coombs ID, Renzi M, Zonouzi M, Farrant M, Cull-Candy SG. Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, gamma-5. Nat Neurosci. 2009 Mar;12(3):277-85. doi: 10.1038/nn.2266. Epub 2009 Feb 22. PMID:19234459 doi:http://dx.doi.org/10.1038/nn.2266
  18. ↑ 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
  19. ↑ Shi Y, Suh YH, Milstein AD, Isozaki K, Schmid SM, Roche KW, Nicoll RA. Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating. Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16315-9. doi:, 10.1073/pnas.1011706107. Epub 2010 Aug 30. PMID:20805473 doi:http://dx.doi.org/10.1073/pnas.1011706107
  20. ↑ Zhao Y, Chen S, Yoshioka C, Baconguis I, Gouaux E. Architecture of fully occupied GluA2 AMPA receptor-TARP complex elucidated by cryo-EM. Nature. 2016 Jul 1. doi: 10.1038/nature18961. PMID:27368053 doi:http://dx.doi.org/10.1038/nature18961

5kk2, resolution 7.30Å

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