Is H95 a pH-dependent gate in aquaporin 4?
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Is H95 a pH-dependent gate in aquaporin 4? / Kaptan, Shreyas; Assentoft, Mette; Schneider, Hans Peter; Fenton, Robert A.; Deitmer, Joachim; MacAulay, Nanna; de Groot, Bert L.
In: Structure, Vol. 23, No. 12, 01.12.2015, p. 2309-2318.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Is H95 a pH-dependent gate in aquaporin 4?
AU - Kaptan, Shreyas
AU - Assentoft, Mette
AU - Schneider, Hans Peter
AU - Fenton, Robert A.
AU - Deitmer, Joachim
AU - MacAulay, Nanna
AU - de Groot, Bert L
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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
AB - 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
U2 - 10.1016/j.str.2015.08.020
DO - 10.1016/j.str.2015.08.020
M3 - Journal article
C2 - 26585511
VL - 23
SP - 2309
EP - 2318
JO - Structure
JF - Structure
SN - 0969-2126
IS - 12
ER -
ID: 143668567