6F7H

Crystal structure of human AQP10

6F7H の概要

• エントリーDOI: 10.2210/pdb6f7h/pdb
• 分子名称: Aquaporin-10, nonyl beta-D-glucopyranoside, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: glycerol, transport protein, aquaporin
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 132587.14

構造登録者

Gotfryd, K.,Wang, K.,Missel, J.W.,Pedersen, P.A.,Gourdon, P. (登録日: 2017-12-08, 公開日: 2018-11-21, 最終更新日: 2024-05-08)

主引用文献

Gotfryd, K.,Mosca, A.F.,Missel, J.W.,Truelsen, S.F.,Wang, K.,Spulber, M.,Krabbe, S.,Helix-Nielsen, C.,Laforenza, U.,Soveral, G.,Pedersen, P.A.,Gourdon, P.
Human adipose glycerol flux is regulated by a pH gate in AQP10.
Nat Commun, 9:4749-4749, 2018

PubMed Abstract: Obesity is a major threat to global health and metabolically associated with glycerol homeostasis. Here we demonstrate that in human adipocytes, the decreased pH observed during lipolysis (fat burning) correlates with increased glycerol release and stimulation of aquaglyceroporin AQP10. The crystal structure of human AQP10 determined at 2.3 Å resolution unveils the molecular basis for pH modulation-an exceptionally wide selectivity (ar/R) filter and a unique cytoplasmic gate. Structural and functional (in vitro and in vivo) analyses disclose a glycerol-specific pH-dependence and pinpoint pore-lining His80 as the pH-sensor. Molecular dynamics simulations indicate how gate opening is achieved. These findings unravel a unique type of aquaporin regulation important for controlling body fat mass. Thus, targeting the cytoplasmic gate to induce constitutive glycerol secretion may offer an attractive option for treating obesity and related complications.

PubMed: 30420639
DOI: 10.1038/s41467-018-07176-z

実験手法

X-RAY DIFFRACTION (2.304 Å)