کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2185611 | 1095994 | 2011 | 14 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Enhancement of Proton Conductance by Mutations of the Selectivity Filter of Aquaporin-1 Enhancement of Proton Conductance by Mutations of the Selectivity Filter of Aquaporin-1](/preview/png/2185611.png)
Prevention of cation permeation in wild-type aquaporin-1 (AQP1) is believed to be associated with the Asn-Pro-Ala (NPA) region and the aromatic/arginine selectivity filter (SF) domain. Previous work has suggested that the NPA region helps to impede proton permeation due to the protein backbone collective macrodipoles that create an environment favoring a directionally discontinuous channel hydrogen-bonded water chain and a large electrostatic barrier. The SF domain contributes to the proton permeation barrier by a spatial restriction mechanism and direct electrostatic interactions. To further explore these various effects, the free-energy barriers and the maximum cation conductance for the permeation of various cations through the AQP1-R195V and AQP1-R195S mutants are predicted computationally. The cations studied included the hydrated excess proton that utilizes the Grotthuss shuttling mechanism, a model “classical” charge localized hydronium cation that exhibits no Grotthuss shuttling, and a sodium cation. The hydrated excess proton was simulated using a specialized multi-state molecular dynamics method including a proper physical treatment of the proton shuttling and charge defect delocalization. Both AQP1 mutants exhibit a surprising cooperative effect leading to a reduction in the free-energy barrier for proton permeation around the NPA region due to altered water configurations in the SF region, with AQP1-R195S having a higher conductance than AQP1-R195V. The theoretical predictions are experimentally confirmed in wild-type AQP1 and the mutants expressed in Xenopus oocytes. The combined results suggest that the SF domain is a specialized structure that has evolved to impede proton permeation in aquaporins.
Graphical AbstractFigure optionsDownload high-quality image (147 K)Download as PowerPoint slideResearch Highlights
► Proton/cation permeation rates calculated in AQP1 mutants.
► Novel cooperative effect found in wild-type channel for blocking proton permeation.
► Computational predictions confirmed by electrophysiology experiments.
► Selectivity filter domain likely evolved to impede proton permeation in aquaporins.
Journal: Journal of Molecular Biology - Volume 407, Issue 4, 8 April 2011, Pages 607–620