PDBsum entry 7cdb

Protein binding

PDB id: 7cdb

Contents

Protein chains

122 a.a.

15 a.a.

Ligands

CIT ×2

ACT

Waters ×84

PDB id:

7cdb

Name:

Protein binding

Title:

Structure of gabarapl1 in complex with gaba(a) receptor gamma 2

Structure:

Gamma-aminobutyric acid receptor-associated protein-like 1. Chain: a, b. Synonym: gaba(a) receptor-associated protein-like 1,glandular epithelial cell protein 1,gec-1. Engineered: yes. Gamma-aminobutyric acid receptor subunit gamma-2. Chain: c. Synonym: gaba(a) receptor subunit gamma-2. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: gabarapl1, apg8l, atg8l, gec1, mncb-0091. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: gabrg2. Expression_system_taxid: 562

Resolution:

1.95Å R-factor: 0.199 R-free: 0.232

Authors:

J.Li,J.Ye,R.Zhu,C.Kong,M.Zhang,C.Wang

Key ref:

J.Ye et al. (2021). Structural basis of GABARAP-mediated GABA_A receptor trafficking and functions on GABAergic synaptic transmission. Nat Commun, 12, 297. PubMed id: 33436612 DOI: 10.1038/s41467-020-20624-z

Date:

19-Jun-20 Release date: 02-Dec-20

Protein chains

Q8R3R8  (GBRL1_MOUSE) -  Gamma-aminobutyric acid receptor-associated protein-like 1 from Mus musculus

Seq: 117 a.a.

Struc: 122 a.a.

Protein chain

P22723  (GBRG2_MOUSE) -  Gamma-aminobutyric acid receptor subunit gamma-2 from Mus musculus

Seq: 474 a.a.

Struc: 15 a.a.

DOI no: 10.1038/s41467-020-20624-z

Nat Commun 12:297 (2021)

PubMed id: 33436612

Structural basis of GABARAP-mediated GABA_A receptor trafficking and functions on GABAergic synaptic transmission.

J.Ye, G.Zou, R.Zhu, C.Kong, C.Miao, M.Zhang, J.Li, W.Xiong, C.Wang.

ABSTRACT

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