7CDB

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

Summary for 7CDB

• Entry DOI: 10.2210/pdb7cdb/pdb
• Descriptor: Gamma-aminobutyric acid receptor-associated protein-like 1, Gamma-aminobutyric acid receptor subunit gamma-2, CITRIC ACID, ... (5 entities in total)
• Functional Keywords: protein binding
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 31812.76

Authors

Li, J.,Ye, J.,Zhu, R.,Kong, C.,Zhang, M.,Wang, C. (deposition date: 2020-06-19, release date: 2020-12-02, Last modification date: 2023-11-29)

Primary citation

Ye, J.,Zou, G.,Zhu, R.,Kong, C.,Miao, C.,Zhang, M.,Li, J.,Xiong, W.,Wang, C.
Structural basis of GABARAP-mediated GABA A receptor trafficking and functions on GABAergic synaptic transmission.
Nat Commun, 12:297-297, 2021

PubMed Abstract: GABA receptors (GABARs) are the primary fast inhibitory ion channels in the central nervous system. Dysfunction of trafficking and localization of GABARs to cell membranes is clinically associated with severe psychiatric disorders in humans. The GABARAP protein is known to support the stability of GABARs 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 γ2 subunit of GABAR. We demonstrate that GABARAP functions to stabilize GABARs via promoting its trafficking pathway instead of blocking receptor endocytosis. The GABARAPL1-γ2-GABAR crystal structure reveals the mechanisms underlying the complex formation. We provide evidence showing that phosphorylation of γ2-GABAR 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-GABAR complex formation. Collectively, our results reveal that GABARAP/GABARAPL1, but not other members of the Atg8 family proteins, specifically regulates synaptic localization of GABARs via modulating the trafficking of the receptor.

PubMed: 33436612
DOI: 10.1038/s41467-020-20624-z

Experimental method

X-RAY DIFFRACTION (1.949 Å)