Loading...
Structural determinants of oligomerization of the aquaporin-4 channel
Kitchen, P Conner, MT Bill, RM Conner, AC
Kitchen, P
Conner, MT
Bill, RM
Conner, AC
Authors
Editors
Other contributors
Affiliation
Epub Date
Issue Date
2016-01-19
Submitted date
Subjects
Animals
Dogs
Humans
Escherichia coli
Water
Recombinant Proteins
Crystallography, X-Ray
Cloning, Molecular
Sequence Alignment
Gene Expression
Amino Acid Sequence
Protein Structure, Secondary
Structural Homology, Protein
Protein Transport
Mutation
Hydrogen Bonding
Osmolar Concentration
Molecular Sequence Data
Aquaporin 1
Aquaporin 3
Aquaporin 4
Protein Interaction Domains and Motifs
Protein Multimerization
Molecular Dynamics Simulation
HEK293 Cells
Madin Darby Canine Kidney Cells
Dogs
Humans
Escherichia coli
Water
Recombinant Proteins
Crystallography, X-Ray
Cloning, Molecular
Sequence Alignment
Gene Expression
Amino Acid Sequence
Protein Structure, Secondary
Structural Homology, Protein
Protein Transport
Mutation
Hydrogen Bonding
Osmolar Concentration
Molecular Sequence Data
Aquaporin 1
Aquaporin 3
Aquaporin 4
Protein Interaction Domains and Motifs
Protein Multimerization
Molecular Dynamics Simulation
HEK293 Cells
Madin Darby Canine Kidney Cells
Alternative
Abstract
©2016 by The American Society for Biochemistry and Molecular Biology, Inc. 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 theAQPfamily.
Citation
Kitchen, P., Conner, M. T., Bill, R. M. and Conner, A. C. (2016) Structural determinants of oligomerization of the aquaporin-4 channel, Journal of Biological Chemistry, 29(13), pp. 6858-6871.
Journal
Research Unit
PubMed ID
26786101
PubMed Central ID
Embedded videos
Additional Links
Type
Journal article
Language
en
Description
Series/Report no.
ISSN
0021-9258
EISSN
1083-351X
ISBN
ISMN
Gov't Doc #
Sponsors
Supported by Biotechnology and Biological Sciences Research Council Grants BB/I019960/1, BB/K013319/1, and BB/L502194/1 and Innovative Medicines Joint Undertaking under Grant Agreement 115583 to the ND4BB ENABLE Consortium.
Rights
Licence for published version: Creative Commons Attribution 4.0 International