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[[Image:2uxa.gif|left|200px]]<br /><applet load="2uxa" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2uxa, resolution 2.38&Aring;" />
'''CRYSTAL STRUCTURE OF THE GLUR2-FLIP LIGAND BINDING DOMAIN, R/G UNEDITED.'''<br />


==Overview==
==Crystal structure of the GluR2-flip ligand binding domain, r/g unedited.==
The subunit composition determines AMPA receptor (AMPA-R) function and, trafficking. Mechanisms underlying channel assembly are thus central to, the efficacy and plasticity of glutamatergic synapses. We previously, showed that RNA editing at the Q/R site of the GluR2 subunit contributes, to the assembly of AMPA-R heteromers by attenuating formation of GluR2, homotetramers. Here we report that this function of the Q/R site depends, on subunit contacts between adjacent ligand binding domains (LBDs)., Changes of LBD interface contacts alter GluR2 assembly properties, forward, traffic, and expression at synapses. Interestingly, developmentally, regulated RNA editing within the LBD (at the R/G site) produces analogous, effects. Our data reveal that editing to glycine reduces the self-assembly, competence of this critical subunit and slows GluR2 maturation in the, endoplasmic reticulum (ER). Therefore, RNA editing sites, located at, strategic subunit interfaces, shape AMPA-R assembly and trafficking in a, developmentally regulated manner.
<StructureSection load='2uxa' size='340' side='right'caption='[[2uxa]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2uxa]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UXA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2uxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uxa OCA], [https://pdbe.org/2uxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uxa RCSB], [https://www.ebi.ac.uk/pdbsum/2uxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uxa ProSAT]</span></td></tr>
</table>
== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ux/2uxa_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2uxa ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The subunit composition determines AMPA receptor (AMPA-R) function and trafficking. Mechanisms underlying channel assembly are thus central to the efficacy and plasticity of glutamatergic synapses. We previously showed that RNA editing at the Q/R site of the GluR2 subunit contributes to the assembly of AMPA-R heteromers by attenuating formation of GluR2 homotetramers. Here we report that this function of the Q/R site depends on subunit contacts between adjacent ligand binding domains (LBDs). Changes of LBD interface contacts alter GluR2 assembly properties, forward traffic, and expression at synapses. Interestingly, developmentally regulated RNA editing within the LBD (at the R/G site) produces analogous effects. Our data reveal that editing to glycine reduces the self-assembly competence of this critical subunit and slows GluR2 maturation in the endoplasmic reticulum (ER). Therefore, RNA editing sites, located at strategic subunit interfaces, shape AMPA-R assembly and trafficking in a developmentally regulated manner.


==About this Structure==
Developmentally regulated, combinatorial RNA processing modulates AMPA receptor biogenesis.,Greger IH, Akamine P, Khatri L, Ziff EB Neuron. 2006 Jul 6;51(1):85-97. PMID:16815334<ref>PMID:16815334</ref>
2UXA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=GLU:'>GLU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:Zn+Binding+Site+For+Residue+A+1263'>AC1</scene>, <scene name='pdbsite=AC2:Zn+Binding+Site+For+Residue+B+1262'>AC2</scene>, <scene name='pdbsite=AC3:Zn+Binding+Site+For+Residue+C+1263'>AC3</scene>, <scene name='pdbsite=AC4:Zn+Binding+Site+For+Residue+B+1263'>AC4</scene>, <scene name='pdbsite=AC5:Zn+Binding+Site+For+Residue+C+1264'>AC5</scene>, <scene name='pdbsite=AC6:GLU+Binding+Site+For+Residue+A+1264'>AC6</scene>, <scene name='pdbsite=AC7:GLU+Binding+Site+For+Residue+C+1265'>AC7</scene> and <scene name='pdbsite=AC8:GLU+Binding+Site+For+Residue+B+1264'>AC8</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UXA OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Developmentally regulated, combinatorial RNA processing modulates AMPA receptor biogenesis., Greger IH, Akamine P, Khatri L, Ziff EB, Neuron. 2006 Jul 6;51(1):85-97. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16815334 16815334]
</div>
<div class="pdbe-citations 2uxa" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: Akamine P]]
[[Category: Akamine, P.]]
[[Category: Greger IH]]
[[Category: Greger, I.H.]]
[[Category: Khatri L]]
[[Category: Khatri, L.]]
[[Category: Ziff EB]]
[[Category: Ziff, E.B.]]
[[Category: GLU]]
[[Category: ZN]]
[[Category: alternative splicing]]
[[Category: ampa]]
[[Category: glur2]]
[[Category: glutamate receptor]]
[[Category: glycoprotein]]
[[Category: ion transport]]
[[Category: ionic channel]]
[[Category: ligand binding domain]]
[[Category: lipoprotein]]
[[Category: membrane]]
[[Category: membrane protein]]
[[Category: palmitate]]
[[Category: phosphorylation]]
[[Category: postsynaptic membrane]]
[[Category: receptor]]
[[Category: rna editing]]
[[Category: transmembrane]]
[[Category: transport]]
 
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