Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF
Xenopus oocytes expressing human aquaporin-7 (AQP7) exhibit greater osmotic water permeability and 3H-glycerol uptake vs. those expressing the bacterial glycerol facilitator GlpF. AQP7-expressing oocytes exposed to increasing extracellular [glycerol] under isosmolal conditions exhibit increasing swe...
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2020.00728/full |
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| author | Fraser J. Moss Paween Mahinthichaichan David T. Lodowski David T. Lodowski Thomas Kowatz Emad Tajkhorshid Andreas Engel Walter F. Boron Walter F. Boron Walter F. Boron Ardeschir Vahedi-Faridi |
| author_facet | Fraser J. Moss Paween Mahinthichaichan David T. Lodowski David T. Lodowski Thomas Kowatz Emad Tajkhorshid Andreas Engel Walter F. Boron Walter F. Boron Walter F. Boron Ardeschir Vahedi-Faridi |
| author_sort | Fraser J. Moss |
| collection | DOAJ |
| description | Xenopus oocytes expressing human aquaporin-7 (AQP7) exhibit greater osmotic water permeability and 3H-glycerol uptake vs. those expressing the bacterial glycerol facilitator GlpF. AQP7-expressing oocytes exposed to increasing extracellular [glycerol] under isosmolal conditions exhibit increasing swelling rates, whereas GlpF-expressing oocytes do not swell at all. To provide a structural basis for these observed physiological differences, we performed X-ray crystallographic structure determination of AQP7 and molecular-dynamics simulations on AQP7 and GlpF. The structure reveals AQP7 tetramers containing two monomers with 3 glycerols, and two monomers with 2 glycerols in the pore. In contrast to GlpF, no glycerol is bound at the AQP7 selectivity filter (SF), comprising residues F74, G222, Y223, and R229. The AQP7 SF is resolved in its closed state because F74 blocks the passage of small solutes. Molecular dynamics simulations demonstrate that F74 undergoes large and rapid conformational changes, allowing glycerol molecules to permeate without orientational restriction. The more rigid GlpF imposes orientational constraints on glycerol molecules passing through the SF. Moreover, GlpF-W48 (analogous to AQP7-F74) undergoes rare but long-lasting conformational changes that block the pore to H2O and glycerol. |
| first_indexed | 2024-04-13T09:57:22Z |
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| id | doaj.art-35f03b2c1ad74f409cf1ec7994cffeba |
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| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-13T09:57:22Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-35f03b2c1ad74f409cf1ec7994cffeba2022-12-22T02:51:19ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-06-011110.3389/fphys.2020.00728518394Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpFFraser J. Moss0Paween Mahinthichaichan1David T. Lodowski2David T. Lodowski3Thomas Kowatz4Emad Tajkhorshid5Andreas Engel6Walter F. Boron7Walter F. Boron8Walter F. Boron9Ardeschir Vahedi-Faridi10Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH, United StatesDepartment of Biochemistry, Center for Biophysics and Quantitative Biology, and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH, United StatesDepartment of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, United StatesDepartment of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH, United StatesDepartment of Biochemistry, Center for Biophysics and Quantitative Biology, and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, United StatesDepartment of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH, United StatesDepartment of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, United StatesDepartment of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH, United StatesDepartment of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH, United StatesXenopus oocytes expressing human aquaporin-7 (AQP7) exhibit greater osmotic water permeability and 3H-glycerol uptake vs. those expressing the bacterial glycerol facilitator GlpF. AQP7-expressing oocytes exposed to increasing extracellular [glycerol] under isosmolal conditions exhibit increasing swelling rates, whereas GlpF-expressing oocytes do not swell at all. To provide a structural basis for these observed physiological differences, we performed X-ray crystallographic structure determination of AQP7 and molecular-dynamics simulations on AQP7 and GlpF. The structure reveals AQP7 tetramers containing two monomers with 3 glycerols, and two monomers with 2 glycerols in the pore. In contrast to GlpF, no glycerol is bound at the AQP7 selectivity filter (SF), comprising residues F74, G222, Y223, and R229. The AQP7 SF is resolved in its closed state because F74 blocks the passage of small solutes. Molecular dynamics simulations demonstrate that F74 undergoes large and rapid conformational changes, allowing glycerol molecules to permeate without orientational restriction. The more rigid GlpF imposes orientational constraints on glycerol molecules passing through the SF. Moreover, GlpF-W48 (analogous to AQP7-F74) undergoes rare but long-lasting conformational changes that block the pore to H2O and glycerol.https://www.frontiersin.org/article/10.3389/fphys.2020.00728/fullAQP7atomic structureglycerol facilitatormolecular dynamics simulationXenopus oocytesosmotic water permeability |
| spellingShingle | Fraser J. Moss Paween Mahinthichaichan David T. Lodowski David T. Lodowski Thomas Kowatz Emad Tajkhorshid Andreas Engel Walter F. Boron Walter F. Boron Walter F. Boron Ardeschir Vahedi-Faridi Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF Frontiers in Physiology AQP7 atomic structure glycerol facilitator molecular dynamics simulation Xenopus oocytes osmotic water permeability |
| title | Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF |
| title_full | Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF |
| title_fullStr | Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF |
| title_full_unstemmed | Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF |
| title_short | Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF |
| title_sort | aquaporin 7 a dynamic aquaglyceroporin with greater water and glycerol permeability than its bacterial homolog glpf |
| topic | AQP7 atomic structure glycerol facilitator molecular dynamics simulation Xenopus oocytes osmotic water permeability |
| url | https://www.frontiersin.org/article/10.3389/fphys.2020.00728/full |
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