Structural determinants of oligomerization of the aquaporin-4 channel


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.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 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).
Uncontrolled Keywords: aquaporin,cellular regulation,oligomerization,protein translocation,water channel,Biochemistry,Cell Biology,Molecular Biology
Publication ISSN: 1083-351X
Last Modified: 15 Apr 2024 07:16
Date Deposited: 16 Feb 2016 09:40
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2016-03-25
Published Online Date: 2016-01-19
Accepted Date: 2016-01-19
Submitted Date: 2015-10-02
Authors: Kitchen, Philip (ORCID Profile 0000-0002-1558-4673)
Conner, Matthew T.
Bill, Roslyn M. (ORCID Profile 0000-0003-1331-0852)
Conner, Alex C.



Version: Published Version

License: Creative Commons Attribution


Version: Accepted Version

Access Restriction: Restricted to Repository staff only

License: Creative Commons Attribution

Export / Share Citation


Additional statistics for this record