Structural determinants of oligomerization of the aquaporin-4 channel

Kitchen, Philip, Conner, Matthew T., Bill, Roslyn M. and Conner, Alex C. (2016). Structural determinants of oligomerization of the aquaporin-4 channel. Journal of Biological Chemistry, 291 (13), pp. 6858-6871.

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.

Publication DOI: https://doi.org/10.1074/jbc.M115.694729
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
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
Full Text Link: http://www.jbc. ... ent/291/13/6858
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2016-03-25
Authors: Kitchen, Philip
Conner, Matthew T.
Bill, Roslyn M. ( 0000-0003-1331-0852)
Conner, Alex C.

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