3QDO

Crystal Structure of PDZ domain of sorting nexin 27 (SNX27) fused to the Gly-Gly linker followed by C-terminal (ESESKV) of GIRK3

3QDO の概要

• エントリーDOI: 10.2210/pdb3qdo/pdb
• 関連するPDBエントリー: 3QE1 3QGL
• 分子名称: Sorting nexin-27, G protein-activated inward rectifier potassium channel 3 chimera (2 entities in total)
• 機能のキーワード: pdz domain, pdz binding, girk3 regulation, early endosomes, brain, neurons, protein binding
• 由来する生物種: Rattus norvegicus (rat); 詳細
• 細胞内の位置: Membrane; Multi-pass membrane protein: Q63511
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11344.75

構造登録者

Balana, B.,Kwiatkowski, W.,Choe, S. (登録日: 2011-01-18, 公開日: 2011-03-16, 最終更新日: 2023-09-13)

主引用文献

Balana, B.,Maslennikov, I.,Kwiatkowski, W.,Stern, K.M.,Bahima, L.,Choe, S.,Slesinger, P.A.
Mechanism underlying selective regulation of G protein-gated inwardly rectifying potassium channels by the psychostimulant-sensitive sorting nexin 27.
Proc.Natl.Acad.Sci.USA, 108:5831-5836, 2011

PubMed Abstract: G protein-gated inwardly rectifying potassium (GIRK) channels are important gatekeepers of neuronal excitability. The surface expression of neuronal GIRK channels is regulated by the psychostimulant-sensitive sorting nexin 27 (SNX27) protein through a class I (-X-Ser/Thr-X-Φ, where X is any residue and Φ is a hydrophobic amino acid) PDZ-binding interaction. The G protein-insensitive inward rectifier channel (IRK1) contains the same class I PDZ-binding motif but associates with a different synaptic PDZ protein, postsynaptic density protein 95 (PSD95). The mechanism by which SNX27 and PSD95 discriminate these channels was previously unclear. Using high-resolution structures coupled with biochemical and functional analyses, we identified key amino acids upstream of the channel's canonical PDZ-binding motif that associate electrostatically with a unique structural pocket in the SNX27-PDZ domain. Changing specific charged residues in the channel's carboxyl terminus or in the PDZ domain converts the selective association and functional regulation by SNX27. Elucidation of this unique interaction site between ion channels and PDZ-containing proteins could provide a therapeutic target for treating brain diseases.

PubMed: 21422294
DOI: 10.1073/pnas.1018645108

実験手法

X-RAY DIFFRACTION (1.88 Å)