5osa

From Proteopedia

(Difference between revisions)

Current revision

GLIC-GABAAR alpha1 chimera crystallized at pH4.6

Structural highlights

5osa is a 5 chain structure with sequence from Gloeobacter violaceus PCC 7421 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7500024Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GBRA1_MOUSE Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:27129275). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:27129275). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (PubMed:27129275). The alpha1/beta2/gamma2 receptor and the alpha1/beta3/gamma2 receptor exhibit synaptogenic activity (PubMed:27129275). GABRA1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (PubMed:25348603). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity).[UniProtKB:P62813]^[1] ^[2] GLIC_GLOVI Cationic channel with similar permeabilities for Na(+) and K(+), that is activated by an increase of the proton concentration on the extracellular side. Displays no permeability for chloride ions. Shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Might contribute to adaptation to external pH change.^[3]

Publication Abstract from PubMed

gamma-Aminobutyric acid receptors (GABAARs) are vital for controlling excitability in the brain. This is emphasized by the numerous neuropsychiatric disorders that result from receptor dysfunction. A critical component of most native GABAARs is the alpha subunit. Its transmembrane domain is the target for many modulators, including endogenous brain neurosteroids that impact anxiety, stress and depression, and for therapeutic drugs, such as general anesthetics. Understanding the basis for the modulation of GABAAR function requires high-resolution structures. Here we present the first atomic structures of a GABAAR chimera at 2.8-A resolution, including those bound with potentiating and inhibitory neurosteroids. These structures define new allosteric binding sites for these modulators that are associated with the alpha-subunit transmembrane domain. Our findings will enable the exploitation of neurosteroids for therapeutic drug design to regulate GABAARs in neurological disorders.

Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites.,Laverty D, Thomas P, Field M, Andersen OJ, Gold MG, Biggin PC, Gielen M, Smart TG Nat Struct Mol Biol. 2017 Oct 2. doi: 10.1038/nsmb.3477. PMID:28967882^[4]

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

References

↑ Swanson AM, Allen AG, Shapiro LP, Gourley SL. GABAAα1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection. Neuropsychopharmacology. 2015 Mar;40(4):1027-36. PMID:25348603 doi:10.1038/npp.2014.292
↑ Brown LE, Nicholson MW, Arama JE, Mercer A, Thomson AM, Jovanovic JN. γ-Aminobutyric Acid Type A (GABAA) Receptor Subunits Play a Direct Structural Role in Synaptic Contact Formation via Their N-terminal Extracellular Domains. J Biol Chem. 2016 Jul 1;291(27):13926-13942. PMID:27129275 doi:10.1074/jbc.M116.714790
↑ Bocquet N, Prado de Carvalho L, Cartaud J, Neyton J, Le Poupon C, Taly A, Grutter T, Changeux JP, Corringer PJ. A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family. Nature. 2007 Jan 4;445(7123):116-9. Epub 2006 Dec 10. PMID:17167423 doi:10.1038/nature05371
↑ Laverty D, Thomas P, Field M, Andersen OJ, Gold MG, Biggin PC, Gielen M, Smart TG. Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites. Nat Struct Mol Biol. 2017 Oct 2. doi: 10.1038/nsmb.3477. PMID:28967882 doi:http://dx.doi.org/10.1038/nsmb.3477

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/5osa"

@@ Line 1: / Line 1: @@
 ==GLIC-GABAAR alpha1 chimera crystallized at pH4.6==
-<StructureSection load='5osa' size='340' side='right' caption='[[5osa]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
+<StructureSection load='5osa' size='340' side='right'caption='[[5osa]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5osa]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OSA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OSA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5osa]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Gloeobacter_violaceus_PCC_7421 Gloeobacter violaceus PCC 7421] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OSA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OSA FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7500024&#8491;</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=5osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5osa OCA], [http://pdbe.org/5osa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5osa RCSB], [http://www.ebi.ac.uk/pdbsum/5osa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5osa ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=5osa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5osa OCA], [https://pdbe.org/5osa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5osa RCSB], [https://www.ebi.ac.uk/pdbsum/5osa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5osa ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GLIC_GLOVI GLIC_GLOVI]] Cationic channel with similar permeabilities for Na(+) and K(+), that is activated by an increase of the proton concentration on the extracellular side. Displays no permeability for chloride ions. Shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Might contribute to adaptation to external pH change.<ref>PMID:17167423</ref>
+[https://www.uniprot.org/uniprot/GBRA1_MOUSE GBRA1_MOUSE] Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:27129275). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:27129275). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (PubMed:27129275). The alpha1/beta2/gamma2 receptor and the alpha1/beta3/gamma2 receptor exhibit synaptogenic activity (PubMed:27129275). GABRA1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (PubMed:25348603). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity).[UniProtKB:P62813]<ref>PMID:25348603</ref> <ref>PMID:27129275</ref> [https://www.uniprot.org/uniprot/GLIC_GLOVI GLIC_GLOVI] Cationic channel with similar permeabilities for Na(+) and K(+), that is activated by an increase of the proton concentration on the extracellular side. Displays no permeability for chloride ions. Shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Might contribute to adaptation to external pH change.<ref>PMID:17167423</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5osa" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ion channels 3D structures|Ion channels 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Gold, M G]]
+[[Category: Gloeobacter violaceus PCC 7421]]
-[[Category: Laverty, D C]]
+[[Category: Large Structures]]
-[[Category: Smart, T G]]
+[[Category: Mus musculus]]
-[[Category: Gabaa-receptor ion channel ion transport extracellular ligand gated ion channel]]
+[[Category: Gold MG]]
-[[Category: Transport protein]]
+[[Category: Laverty DC]]
+[[Category: Smart TG]]

5osa

From Proteopedia

Current revision

GLIC-GABAAR alpha1 chimera crystallized at pH4.6

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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