Water channel pore size determines exclusion properties but not solute selectivity
Authors
Kitchen, PhilipSalman, Mootaz M
Pickel, Simone U
Jennings, Jordan
Törnroth-Horsefield, Susanna
Conner, Matthew T
Bill, Roslyn M
Conner, Alex C
Issue Date
2019-12-30
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Show full item recordAbstract
Aquaporins (AQPs) are a ubiquitous family of transmembrane water channel proteins. A subgroup of AQP water channels also facilitates transmembrane diffusion of small, polar solutes. A constriction within the pore, the aromatic/arginine (ar/R) selectivity filter, is thought to control solute permeability: previous studies on single representative water channel proteins suggest narrow channels conduct water, whilst wider channels permit passage of solutes. To assess this model of selectivity, we used mutagenesis, permeability measurements and in silico comparisons of water-specific as well as glycerol-permeable human AQPs. Our studies show that single amino acid substitutions in the selectivity filters of AQP1, AQP4 and AQP3 differentially affect glycerol and urea permeability in an AQP-specific manner. Comparison between in silico-calculated channel cross-sectional areas and in vitro permeability measurements suggests that selectivity filter cross-sectional area predicts urea but not glycerol permeability. Our data show that substrate discrimination in water channels depends on a complex interplay between the solute, pore size, and polarity, and that using single water channel proteins as representative models has led to an underestimation of this complexity.Citation
Kitchen, P., Salman, M.M., Pickel, S.U. et al. (2019) Water channel pore size determines exclusion properties but not solute selectivity, Science Reports, 9, 20369, doi:10.1038/s41598-019-56814-zPublisher
Springer Science and Business Media LLCJournal
Scientific ReportsAdditional Links
https://www.nature.com/articles/s41598-019-56814-zType
Journal articleLanguage
enISSN
2045-2322EISSN
2045-2322ae974a485f413a2113503eed53cd6c53
10.1038/s41598-019-56814-z
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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/