4f12: Difference between revisions
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==Crystal structure of the extracellular domain of human GABA(B) receptor GBR2== | |||
<StructureSection load='4f12' size='340' side='right' caption='[[4f12]], [[Resolution|resolution]] 3.02Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4f12]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F12 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F12 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=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f11|4f11]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GABBR2, GPR51, GPRC3B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4f12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f12 OCA], [http://pdbe.org/4f12 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f12 RCSB], [http://www.ebi.ac.uk/pdbsum/4f12 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f12 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/GABR2_HUMAN GABR2_HUMAN]] Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception.<ref>PMID:9872316</ref> <ref>PMID:10328880</ref> <ref>PMID:18165688</ref> <ref>PMID:22660477</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Inhibitory neurotransmission is mediated primarily by GABA. The metabotropic GABA(B) receptor is a G protein-coupled receptor central to mammalian brain function. Malfunction of GABA(B) receptor has been implicated in several neurological disorders. GABA(B) receptor functions as a heterodimeric assembly of GBR1 and GBR2 subunits, where GBR1 is responsible for ligand-binding and GBR2 is responsible for G protein coupling. Here we demonstrate that the GBR2 ectodomain directly interacts with the GBR1 ectodomain to increase agonist affinity by selectively stabilizing the agonist-bound conformation of GBR1. We present the crystal structure of the GBR2 ectodomain, which reveals a polar heterodimeric interface. We also identify specific heterodimer contacts from both subunits, and GBR1 residues involved in ligand recognition. Lastly, our structural and functional data indicate that the GBR2 ectodomain adopts a constitutively open conformation, suggesting a structural asymmetry in the active state of GABA(B) receptor that is unique to the GABAergic system. | |||
Structure and functional interaction of the extracellular domain of human GABA(B) receptor GBR2.,Geng Y, Xiong D, Mosyak L, Malito DL, Kniazeff J, Chen Y, Burmakina S, Quick M, Bush M, Javitch JA, Pin JP, Fan QR Nat Neurosci. 2012 Jun 3;15(7):970-8. doi: 10.1038/nn.3133. PMID:22660477<ref>PMID:22660477</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4f12" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
[[ | *[[GABA receptor|GABA receptor]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Burmakina, S | [[Category: Human]] | ||
[[Category: Bush, M | [[Category: Burmakina, S]] | ||
[[Category: Chen, Y | [[Category: Bush, M]] | ||
[[Category: Fan, Q R | [[Category: Chen, Y]] | ||
[[Category: Geng, Y | [[Category: Fan, Q R]] | ||
[[Category: Javitch, J A | [[Category: Geng, Y]] | ||
[[Category: Kniazeff, J | [[Category: Javitch, J A]] | ||
[[Category: Malito, D L | [[Category: Kniazeff, J]] | ||
[[Category: Mosyak, L | [[Category: Malito, D L]] | ||
[[Category: Pin, J P | [[Category: Mosyak, L]] | ||
[[Category: Quick, M | [[Category: Pin, J P]] | ||
[[Category: Xiong, D | [[Category: Quick, M]] | ||
[[Category: Xiong, D]] | |||
[[Category: G-protein coupled receptor]] | [[Category: G-protein coupled receptor]] | ||
[[Category: Signaling protein]] | [[Category: Signaling protein]] | ||
[[Category: Venus flytrap module]] | [[Category: Venus flytrap module]] | ||
Revision as of 15:18, 4 August 2016
Crystal structure of the extracellular domain of human GABA(B) receptor GBR2Crystal structure of the extracellular domain of human GABA(B) receptor GBR2
Structural highlights
Function[GABR2_HUMAN] Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception.[1] [2] [3] [4] Publication Abstract from PubMedInhibitory neurotransmission is mediated primarily by GABA. The metabotropic GABA(B) receptor is a G protein-coupled receptor central to mammalian brain function. Malfunction of GABA(B) receptor has been implicated in several neurological disorders. GABA(B) receptor functions as a heterodimeric assembly of GBR1 and GBR2 subunits, where GBR1 is responsible for ligand-binding and GBR2 is responsible for G protein coupling. Here we demonstrate that the GBR2 ectodomain directly interacts with the GBR1 ectodomain to increase agonist affinity by selectively stabilizing the agonist-bound conformation of GBR1. We present the crystal structure of the GBR2 ectodomain, which reveals a polar heterodimeric interface. We also identify specific heterodimer contacts from both subunits, and GBR1 residues involved in ligand recognition. Lastly, our structural and functional data indicate that the GBR2 ectodomain adopts a constitutively open conformation, suggesting a structural asymmetry in the active state of GABA(B) receptor that is unique to the GABAergic system. Structure and functional interaction of the extracellular domain of human GABA(B) receptor GBR2.,Geng Y, Xiong D, Mosyak L, Malito DL, Kniazeff J, Chen Y, Burmakina S, Quick M, Bush M, Javitch JA, Pin JP, Fan QR Nat Neurosci. 2012 Jun 3;15(7):970-8. doi: 10.1038/nn.3133. PMID:22660477[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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