4HPF

Structure of the human SLO3 gating ring

4HPF の概要

• エントリーDOI: 10.2210/pdb4hpf/pdb
• 分子名称: Potassium channel subfamily U member 1 (1 entity in total)
• 機能のキーワード: potassium channel, ph-gated, membrane protein, transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane ; Multi-pass membrane protein : A8MYU2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 162441.38

構造登録者

Leonetti, M.D.,Yuan, P.,MacKinnon, R. (登録日: 2012-10-23, 公開日: 2012-11-07, 最終更新日: 2023-09-20)

主引用文献

Leonetti, M.D.,Yuan, P.,Hsiung, Y.,Mackinnon, R.
Functional and structural analysis of the human SLO3 pH- and voltage-gated K+ channel.
Proc.Natl.Acad.Sci.USA, 109:19274-19279, 2012

PubMed Abstract: The activation of eukaryotic SLO K(+) channels by intracellular cues, mediated by a cytoplasmic structure called the gating ring, is central to their physiological roles. SLO3 channels are exclusively expressed in mammalian sperm, where variations of intracellular pH are critical to cellular function. Previous studies primarily focused on the mouse SLO3 orthologue and revealed that, in murine sperm, SLO3 mediates a voltage- and alkalization-activated K(+) current essential to male fertility. Here we investigate the activation of the human SLO3 channel by intracellular pH at the functional and structural level. By using electrophysiology in a heterologous system, we show that human SLO3 opens upon intracellular pH increase and that its expression and functional properties are modulated by LRRC52, a testis-specific accessory subunit. We next present the crystal structure of the human SLO3 gating ring. Comparison with the known structures of the corresponding domain from SLO1, a Ca(2+)-activated homologue, suggests that the SLO3 gating ring structure may represent an open state. Together, these results present insights into the function of a protein expected to be critical for human reproduction and provide a framework to study the mechanism of pH gating in SLO3 channels.

PubMed: 23129643
DOI: 10.1073/pnas.1215078109

実験手法

X-RAY DIFFRACTION (3.4 Å)