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6f7h
From Proteopedia
Crystal structure of human AQP10
Structural highlights
FunctionAQP10_HUMAN Water channel that mediates water transport across cell membranes irrespective of the cytosolic pH (PubMed:12084581, PubMed:21733844, PubMed:23382902, PubMed:30420639). The channel is permeable to glycerol, especially when the cytosolic pH is acidified (PubMed:21733844, PubMed:30420639). Contributes to adipocyte water and glycerol permeability, and may thereby contribute to the utilization of glycerol derived from phospholipid degradation (PubMed:23382902). May contribute to water transport in the intestine (Probable).[1] [2] [3] [4] [5] [6] [7] Water channel that mediates water transport across cell membranes, but that is not permeable to glycerol.[8] Publication Abstract from PubMedObesity 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 A 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. Human adipose glycerol flux is regulated by a pH gate in AQP10.,Gotfryd K, Mosca AF, Missel JW, Truelsen SF, Wang K, Spulber M, Krabbe S, Helix-Nielsen C, Laforenza U, Soveral G, Pedersen PA, Gourdon P Nat Commun. 2018 Nov 12;9(1):4749. doi: 10.1038/s41467-018-07176-z. PMID:30420639[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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