Structural determinants of oligomerization of the aquaporin-4 channel

Philip Kitchen, Matthew T. Conner, Roslyn M. Bill, Alex C. Conner*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The aquaporins (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.

Original languageEnglish
Pages (from-to)6858-6871
Number of pages14
JournalJournal of Biological Chemistry
Volume291
Issue number13
Early online date19 Jan 2016
DOIs
Publication statusPublished - 25 Mar 2016

Fingerprint

Aquaporin 4
Oligomerization
Aquaporins
Permeability
Water
Molecular Dynamics Simulation
Hydrogen Bonding
Cell membranes
Ion Channels
Molecular dynamics
Hydrogen bonds
Membrane Proteins
Cell Membrane
Mutation
Computer simulation

Bibliographical note

© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Final version free via Creative Commons CC-BY license.

Funding: EPSRC (EP/F500378/1); BBSRC (BB/I019960/1, BB/K013319/1 and BB/L502194/1); and Innovative Medicines Joint Undertaking (115583).

Keywords

  • aquaporin
  • cellular regulation
  • oligomerization
  • protein translocation
  • water channel

Cite this

Kitchen, Philip ; Conner, Matthew T. ; Bill, Roslyn M. ; Conner, Alex C. / Structural determinants of oligomerization of the aquaporin-4 channel. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 13. pp. 6858-6871.
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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.

Research output: Contribution to journalArticle

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