7cdb | pdb_00007cdb

Structure of GABARAPL1 in complex with GABA(A) receptor gamma 2

spinqualitylabelsall models 7cdb, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7cdb is a 3 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.949Å Ligands: ACT, CIT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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). 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also GABA receptor 3D structures GABA receptor-associated protein 3D structures

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