Structural Determinants of Oligomerization of the Aquaporin-4 Channel

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Structural Determinants of Oligomerization of the Aquaporin-4 Channel. / Kitchen, Philip; Conner, Matthew T; Bill, Roslyn M; Conner, Alex C.

In: Journal of Biological Chemistry, Vol. 291, No. 13, 25.03.2016, p. 6858-6871.

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@article{3c0d4645cbcd4eb681226412a1f90035,
title = "Structural Determinants of Oligomerization of the Aquaporin-4 Channel",
abstract = "The aquaporin (AQP) family of integral membrane protein channels mediate cellular water and solute flow. Although qualitative and quantitative differences in channel permeability, selectivity, subcellular localization, and trafficking responses have been observed for different members of the AQP family, the signature homotetrameric quaternary structure is conserved. Using a variety of biophysical techniques, we show that mutations to an intracellular loop (loop D) of human AQP4 reduce oligomerization. Non-tetrameric AQP4 mutants are unable to relocalize to the plasma membrane in response to changes in extracellular tonicity, despite equivalent constitutive surface expression levels and water permeability to wild-type AQP4. A network of AQP4 loop D hydrogen bonding interactions, identified using molecular dynamics simulations and based on a comparative mutagenic analysis of AQPs 1, 3, and 4, suggest that loop D interactions may provide a general structural framework for tetrameric assembly within the AQP family.",
author = "Philip Kitchen and Conner, {Matthew T} and Bill, {Roslyn M} and Conner, {Alex C}",
note = "{\textcopyright} 2016 by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2016",
month = mar
day = "25",
doi = "10.1074/jbc.M115.694729",
language = "English",
volume = "291",
pages = "6858--6871",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology",
number = "13",

}

RIS

TY - JOUR

T1 - Structural Determinants of Oligomerization of the Aquaporin-4 Channel

AU - Kitchen, Philip

AU - Conner, Matthew T

AU - Bill, Roslyn M

AU - Conner, Alex C

N1 - © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2016/3/25

Y1 - 2016/3/25

N2 - The aquaporin (AQP) family of integral membrane protein channels mediate cellular water and solute flow. Although qualitative and quantitative differences in channel permeability, selectivity, subcellular localization, and trafficking responses have been observed for different members of the AQP family, the signature homotetrameric quaternary structure is conserved. Using a variety of biophysical techniques, we show that mutations to an intracellular loop (loop D) of human AQP4 reduce oligomerization. Non-tetrameric AQP4 mutants are unable to relocalize to the plasma membrane in response to changes in extracellular tonicity, despite equivalent constitutive surface expression levels and water permeability to wild-type AQP4. A network of AQP4 loop D hydrogen bonding interactions, identified using molecular dynamics simulations and based on a comparative mutagenic analysis of AQPs 1, 3, and 4, suggest that loop D interactions may provide a general structural framework for tetrameric assembly within the AQP family.

AB - The aquaporin (AQP) family of integral membrane protein channels mediate cellular water and solute flow. Although qualitative and quantitative differences in channel permeability, selectivity, subcellular localization, and trafficking responses have been observed for different members of the AQP family, the signature homotetrameric quaternary structure is conserved. Using a variety of biophysical techniques, we show that mutations to an intracellular loop (loop D) of human AQP4 reduce oligomerization. Non-tetrameric AQP4 mutants are unable to relocalize to the plasma membrane in response to changes in extracellular tonicity, despite equivalent constitutive surface expression levels and water permeability to wild-type AQP4. A network of AQP4 loop D hydrogen bonding interactions, identified using molecular dynamics simulations and based on a comparative mutagenic analysis of AQPs 1, 3, and 4, suggest that loop D interactions may provide a general structural framework for tetrameric assembly within the AQP family.

U2 - 10.1074/jbc.M115.694729

DO - 10.1074/jbc.M115.694729

M3 - Article

C2 - 26786101

VL - 291

SP - 6858

EP - 6871

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 13

ER -