Water channel pore size determines exclusion properties but not solute selectivity

Philip Kitchen*, Mootaz M. Salman, Simone Pickel, Jordan Jennings, Susanna Törnroth-horsefield, Matthew Conner, Roslyn Bill, Alex C. Conner

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Article number20369
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 30 Dec 2019

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solute
permeability
water
filter
urea
protein
substitution
amino acid
substrate

Bibliographical note

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Funding: Engineering and Physical Sciences Research Council EP/F500378/1, UK Biotechnology and Biosciences Research Council BB BB/P025927/1, HCED grant number GD-13-13

Cite this

Kitchen, P., Salman, M. M., Pickel, S., Jennings, J., Törnroth-horsefield, S., Conner, M., ... Conner, A. C. (2019). Water channel pore size determines exclusion properties but not solute selectivity. Scientific Reports, 9(1), [20369]. https://doi.org/10.1038/s41598-019-56814-z
Kitchen, Philip ; Salman, Mootaz M. ; Pickel, Simone ; Jennings, Jordan ; Törnroth-horsefield, Susanna ; Conner, Matthew ; Bill, Roslyn ; Conner, Alex C. / Water channel pore size determines exclusion properties but not solute selectivity. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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Kitchen, P, Salman, MM, Pickel, S, Jennings, J, Törnroth-horsefield, S, Conner, M, Bill, R & Conner, AC 2019, 'Water channel pore size determines exclusion properties but not solute selectivity', Scientific Reports, vol. 9, no. 1, 20369. https://doi.org/10.1038/s41598-019-56814-z

Water channel pore size determines exclusion properties but not solute selectivity. / Kitchen, Philip; Salman, Mootaz M.; Pickel, Simone; Jennings, Jordan; Törnroth-horsefield, Susanna; Conner, Matthew; Bill, Roslyn; Conner, Alex C.

In: Scientific Reports, Vol. 9, No. 1, 20369, 30.12.2019.

Research output: Contribution to journalArticle

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Kitchen P, Salman MM, Pickel S, Jennings J, Törnroth-horsefield S, Conner M et al. Water channel pore size determines exclusion properties but not solute selectivity. Scientific Reports. 2019 Dec 30;9(1). 20369. https://doi.org/10.1038/s41598-019-56814-z