5o8f

From Proteopedia

(Difference between revisions)

Current revision

Structure of a chimaeric beta3-alpha5 GABAA receptor in complex with nanobody Nb25 and pregnanolone

Structural highlights

5o8f is a 10 chain structure with sequence from Homo sapiens and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GBRB3_HUMAN Autism;Childhood absence epilepsy. Disease susceptibility is associated with variations affecting the gene represented in this entry.

Function

GBRB3_HUMAN GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.GBRA5_HUMAN GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

Publication Abstract from PubMed

Type A gamma-aminobutyric acid receptors (GABAARs) are the principal mediators of inhibitory neurotransmission in the human brain. Endogenous neurosteroids interact with GABAARs to regulate acute and chronic anxiety and are potent sedative, analgesic, anticonvulsant and anesthetic agents. Their mode of binding and mechanism of receptor potentiation, however, remain unknown. Here we report crystal structures of a chimeric GABAAR construct in apo and pregnanolone-bound states. The neurosteroid-binding site is mechanically coupled to the helices lining the ion channel pore and modulates the desensitization-gate conformation. We demonstrate that the equivalent site is responsible for physiological, heteromeric GABAAR potentiation and explain the contrasting modulatory properties of 3a versus 3b neurosteroid epimers. These results illustrate how peripheral lipid ligands can regulate the desensitization gate of GABAARs, a process of broad relevance to pentameric ligand-gated ion channels.

Structural basis for GABAA receptor potentiation by neurosteroids.,Miller PS, Scott S, Masiulis S, De Colibus L, Pardon E, Steyaert J, Aricescu AR Nat Struct Mol Biol. 2017 Oct 9. doi: 10.1038/nsmb.3484. PMID:28991263^[1]

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

References

↑ Miller PS, Scott S, Masiulis S, De Colibus L, Pardon E, Steyaert J, Aricescu AR. Structural basis for GABAA receptor potentiation by neurosteroids. Nat Struct Mol Biol. 2017 Oct 9. doi: 10.1038/nsmb.3484. PMID:28991263 doi:http://dx.doi.org/10.1038/nsmb.3484

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5o8f"

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[5o8f]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O8F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O8F 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]] 3.2&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P9N:Pregnanolone'>P9N</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P9N:1-[(3~{R},5~{R},8~{R},9~{S},10~{S},13~{S},14~{S},17~{S})-10,13-dimethyl-3-oxidanyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1~{H}-cyclopenta[a]phenanthren-17-yl]ethanone'>P9N</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=5o8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o8f OCA], [https://pdbe.org/5o8f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o8f RCSB], [https://www.ebi.ac.uk/pdbsum/5o8f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o8f ProSAT]</span></td></tr>
 </table>

5o8f

From Proteopedia

Current revision

Structure of a chimaeric beta3-alpha5 GABAA receptor in complex with nanobody Nb25 and pregnanolone

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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