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4f11

From Proteopedia

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Crystal structure of the extracellular domain of human GABA(B) receptor GBR2

Structural highlights

4f11 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[5]

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

References

↑ White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH. Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature. 1998 Dec 17;396(6712):679-82. PMID:9872316 doi:http://dx.doi.org/10.1038/25354
↑ Martin SC, Russek SJ, Farb DH. Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1. Mol Cell Neurosci. 1999 Mar;13(3):180-91. PMID:10328880 doi:http://dx.doi.org/S1044-7431(99)90741-8
↑ Nomura R, Suzuki Y, Kakizuka A, Jingami H. Direct detection of the interaction between recombinant soluble extracellular regions in the heterodimeric metabotropic gamma-aminobutyric acid receptor. J Biol Chem. 2008 Feb 22;283(8):4665-73. doi: 10.1074/jbc.M705202200. Epub 2007, Dec 28. PMID:18165688 doi:http://dx.doi.org/10.1074/jbc.M705202200
↑ Geng Y, Xiong D, Mosyak L, Malito DL, Kniazeff J, Chen Y, Burmakina S, Quick M, Bush M, Javitch JA, Pin JP, Fan QR. Structure and functional interaction of the extracellular domain of human GABA(B) receptor GBR2. Nat Neurosci. 2012 Jun 3;15(7):970-8. doi: 10.1038/nn.3133. PMID:22660477 doi:10.1038/nn.3133
↑ Geng Y, Xiong D, Mosyak L, Malito DL, Kniazeff J, Chen Y, Burmakina S, Quick M, Bush M, Javitch JA, Pin JP, Fan QR. Structure and functional interaction of the extracellular domain of human GABA(B) receptor GBR2. Nat Neurosci. 2012 Jun 3;15(7):970-8. doi: 10.1038/nn.3133. PMID:22660477 doi:10.1038/nn.3133

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4f11"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the extracellular domain of human GABA(B) receptor GBR2==
-<StructureSection load='4f11' size='340' side='right' caption='[[4f11]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
+<StructureSection load='4f11' size='340' side='right'caption='[[4f11]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4f11]] 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=4F11 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F11 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4f11]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F11 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F11 FirstGlance]. <br>
-</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>
+</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=4f11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f11 OCA], [https://pdbe.org/4f11 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f11 RCSB], [https://www.ebi.ac.uk/pdbsum/4f11 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f11 ProSAT]</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=4f11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f11 OCA], [http://pdbe.org/4f11 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f11 RCSB], [http://www.ebi.ac.uk/pdbsum/4f11 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f11 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>
+[https://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 ==
@@ Line 20: / Line 19: @@
 ==See Also==
-*[[GABA receptor|GABA receptor]]
+*[[GABA receptor 3D structures|GABA receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Burmakina, S]]
+[[Category: Large Structures]]
-[[Category: Bush, M]]
+[[Category: Burmakina S]]
-[[Category: Chen, Y]]
+[[Category: Bush M]]
-[[Category: Fan, Q R]]
+[[Category: Chen Y]]
-[[Category: Geng, Y]]
+[[Category: Fan QR]]
-[[Category: Javitch, J A]]
+[[Category: Geng Y]]
-[[Category: Kniazeff, J]]
+[[Category: Javitch JA]]
-[[Category: Malito, D L]]
+[[Category: Kniazeff J]]
-[[Category: Mosyak, L]]
+[[Category: Malito DL]]
-[[Category: Pin, J P]]
+[[Category: Mosyak L]]
-[[Category: Quick, M]]
+[[Category: Pin J-P]]
-[[Category: Xiong, D]]
+[[Category: Quick M]]
-[[Category: G-protein coupled receptor]]
+[[Category: Xiong D]]
-[[Category: Signaling protein]]
-[[Category: Venus flytrap module]]

4f11

From Proteopedia

Current revision

Crystal structure of the extracellular domain of human GABA(B) receptor GBR2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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