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Structure. 2015 Dec 1;23(12):2309-2318. doi: 10.1016/j.str.2015.08.020. Epub 2015 Nov 12.

H95 Is a pH-Dependent Gate in Aquaporin 4.

Author information

1
Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
2
Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, The Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
3
Division of General Zoology, Department of Biology, University of Kaiserslautern, 67653 Kaiserslautern, Germany.
4
Department of Biomedicine, InterPrET Center, Aarhus University, Nordre Ringgade 1, 8000 Aarhus C, Denmark.
5
Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: bgroot@gwdg.de.

Abstract

Aquaporin 4 (AQP4) is a transmembrane protein from the aquaporin family and is the predominant water channel in the mammalian brain. The regulation of permeability of this protein could be of potential therapeutic use to treat various forms of damage to the nervous tissue. In this work, based on data obtained from in silico and in vitro studies, a pH sensitivity that regulates the osmotic water permeability of AQP4 is demonstrated. The results indicate that AQP4 has increased water permeability at conditions of low pH in atomistic computer simulations and experiments carried out on Xenopus oocytes expressing AQP4. With molecular dynamics simulations, this effect was traced to a histidine residue (H95) located in the cytoplasmic lumen of AQP4. A mutant form of AQP4, in which H95 was replaced with an alanine (H95A), loses sensitivity to cytoplasmic pH changes in in vitro osmotic water permeability, thereby substantiating the in silico work.

PMID:
26585511
DOI:
10.1016/j.str.2015.08.020
[Indexed for MEDLINE]
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