7cdb: Difference between revisions
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The | ==Structure of GABARAPL1 in complex with GABA(A) receptor gamma 2== | ||
<StructureSection load='7cdb' size='340' side='right'caption='[[7cdb]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7cdb]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CDB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CDB 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]] 1.949Å</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=CIT:CITRIC+ACID'>CIT</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=7cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cdb OCA], [https://pdbe.org/7cdb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cdb RCSB], [https://www.ebi.ac.uk/pdbsum/7cdb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cdb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GBRL1_MOUSE GBRL1_MOUSE] Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
GABA(A) receptors (GABA(A)Rs) are the primary fast inhibitory ion channels in the central nervous system. Dysfunction of trafficking and localization of GABA(A)Rs to cell membranes is clinically associated with severe psychiatric disorders in humans. The GABARAP protein is known to support the stability of GABA(A)Rs in synapses, but the underlying molecular mechanisms remain to be elucidated. Here, we show that GABARAP/GABARAPL1 directly binds to a previously unappreciated region in the gamma2 subunit of GABA(A)R. We demonstrate that GABARAP functions to stabilize GABA(A)Rs via promoting its trafficking pathway instead of blocking receptor endocytosis. The GABARAPL1-gamma2-GABA(A)R crystal structure reveals the mechanisms underlying the complex formation. We provide evidence showing that phosphorylation of gamma2-GABA(A)R differentially modulate the receptor's binding to GABARAP and the clathrin adaptor protein AP2. Finally, we demonstrate that GABAergic synaptic currents are reduced upon specific blockage of the GABARAP-GABA(A)R complex formation. Collectively, our results reveal that GABARAP/GABARAPL1, but not other members of the Atg8 family proteins, specifically regulates synaptic localization of GABA(A)Rs via modulating the trafficking of the receptor. | |||
Structural basis of GABARAP-mediated GABA(A) receptor trafficking and functions on GABAergic synaptic transmission.,Ye J, Zou G, Zhu R, Kong C, Miao C, Zhang M, Li J, Xiong W, Wang C Nat Commun. 2021 Jan 12;12(1):297. doi: 10.1038/s41467-020-20624-z. PMID:33436612<ref>PMID:33436612</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7cdb" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[GABA receptor 3D structures|GABA receptor 3D structures]] | |||
*[[GABA receptor-associated protein 3D structures|GABA receptor-associated protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Kong C]] | |||
[[Category: Li J]] | |||
[[Category: Wang C]] | |||
[[Category: Ye J]] | |||
[[Category: Zhang M]] | |||
[[Category: Zhu R]] | |||
Latest revision as of 19:05, 29 November 2023
Structure of GABARAPL1 in complex with GABA(A) receptor gamma 2Structure of GABARAPL1 in complex with GABA(A) receptor gamma 2
Structural highlights
FunctionGBRL1_MOUSE Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (By similarity). Publication Abstract from PubMedGABA(A) receptors (GABA(A)Rs) are the primary fast inhibitory ion channels in the central nervous system. Dysfunction of trafficking and localization of GABA(A)Rs to cell membranes is clinically associated with severe psychiatric disorders in humans. The GABARAP protein is known to support the stability of GABA(A)Rs in synapses, but the underlying molecular mechanisms remain to be elucidated. Here, we show that GABARAP/GABARAPL1 directly binds to a previously unappreciated region in the gamma2 subunit of GABA(A)R. We demonstrate that GABARAP functions to stabilize GABA(A)Rs via promoting its trafficking pathway instead of blocking receptor endocytosis. The GABARAPL1-gamma2-GABA(A)R crystal structure reveals the mechanisms underlying the complex formation. We provide evidence showing that phosphorylation of gamma2-GABA(A)R differentially modulate the receptor's binding to GABARAP and the clathrin adaptor protein AP2. Finally, we demonstrate that GABAergic synaptic currents are reduced upon specific blockage of the GABARAP-GABA(A)R complex formation. Collectively, our results reveal that GABARAP/GABARAPL1, but not other members of the Atg8 family proteins, specifically regulates synaptic localization of GABA(A)Rs via modulating the trafficking of the receptor. Structural basis of GABARAP-mediated GABA(A) receptor trafficking and functions on GABAergic synaptic transmission.,Ye J, Zou G, Zhu R, Kong C, Miao C, Zhang M, Li J, Xiong W, Wang C Nat Commun. 2021 Jan 12;12(1):297. doi: 10.1038/s41467-020-20624-z. PMID:33436612[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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