6M8R

Crystal structure of the KCTD16 BTB domain in complex with GABAB2 peptide

6M8R の概要

• エントリーDOI: 10.2210/pdb6m8r/pdb
• 関連するPDBエントリー: 6M8S
• 分子名称: BTB/POZ domain-containing protein KCTD16, Gamma-aminobutyric acid type B receptor subunit 2, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: pentamer, btb domain, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 131289.99

構造登録者

Zheng, S.,Kruse, A.C. (登録日: 2018-08-22, 公開日: 2019-02-27, 最終更新日: 2023-10-11)

主引用文献

Zheng, S.,Abreu, N.,Levitz, J.,Kruse, A.C.
Structural basis for KCTD-mediated rapid desensitization of GABABsignalling.
Nature, 567:127-131, 2019

PubMed Abstract: The GABA (γ-aminobutyric acid type B) receptor is one of the principal inhibitory neurotransmitter receptors in the brain, and it signals through heterotrimeric G proteins to activate a variety of effectors, including G-protein-coupled inwardly rectifying potassium channels (GIRKs). GABA-receptor signalling is tightly regulated by auxiliary subunits called KCTDs, which control the kinetics of GIRK activation and desensitization. However, the mechanistic basis for KCTD modulation of GABA signalling remains incompletely understood. Here, using a combination of X-ray crystallography, electron microscopy, and functional and biochemical experiments, we reveal the molecular details of KCTD binding to both GABA receptors and G-protein βγ subunits. KCTDs associate with the receptor by forming an asymmetric pentameric ring around a region of the receptor carboxy-terminal tail, while a second KCTD domain, H1, engages in a symmetric interaction with five copies of Gβγ in which the G-protein subunits also interact directly with one another. We further show that KCTD binding to Gβγ is highly cooperative, defining a model in which KCTD proteins cooperatively strip G proteins from GIRK channels to induce rapid desensitization following receptor activation. These results provide a framework for understanding the molecular basis for the precise temporal control of GABA signalling by KCTD proteins.

PubMed: 30814734
DOI: 10.1038/s41586-019-0990-0

実験手法

X-RAY DIFFRACTION (3.2 Å)