Role of Pore-Lining Residues in Defining the Rate of Water Conduction by Aquaporin-0

Patrick O. Saboe, Chiara Rapisarda, Shreyas Kaptan, Yu Shan Hsiao, Samantha R. Summers, Rita De Zorzi, Danijela Dukovski, Jiaheng Yu, Bert L. de Groot, Manish Kumar, Thomas Walz

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5 Scopus citations

Abstract

Compared to other aquaporins (AQPs), lens-specific AQP0 is a poor water channel, and its permeability was reported to be pH-dependent. To date, most water conduction studies on AQP0 were performed on protein expressed in Xenopus oocytes, and the results may therefore also reflect effects introduced by the oocytes themselves. Experiments with purified AQP0 reconstituted into liposomes are challenging because the water permeability of AQP0 is only slightly higher than that of pure lipid bilayers. By reconstituting high amounts of AQP0 and using high concentrations of cholesterol to reduce the permeability of the lipid bilayer, we improved the signal-to-noise ratio of water permeability measurements on AQP0 proteoliposomes. Our measurements show that mutation of two pore-lining tyrosine residues, Tyr-23 and Tyr-149 in sheep AQP0, to the corresponding residues in the high-permeability water channel AQP1 have additive effects and together increase the water permeability of AQP0 40-fold to a level comparable to that of AQP1. Molecular dynamics simulations qualitatively support these experimental findings and suggest that mutation of Tyr-23 changes the pore profile at the gate formed by residue Arg-187.

Original languageEnglish (US)
Pages (from-to)953-965
Number of pages13
JournalBiophysical journal
Volume112
Issue number5
DOIs
StatePublished - Mar 14 2017

All Science Journal Classification (ASJC) codes

  • Biophysics

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    Saboe, P. O., Rapisarda, C., Kaptan, S., Hsiao, Y. S., Summers, S. R., De Zorzi, R., Dukovski, D., Yu, J., de Groot, B. L., Kumar, M., & Walz, T. (2017). Role of Pore-Lining Residues in Defining the Rate of Water Conduction by Aquaporin-0. Biophysical journal, 112(5), 953-965. https://doi.org/10.1016/j.bpj.2017.01.026