The selectivity of the Na+/K+-pump is controlled by binding site protonation and self-correcting occlusion
The Na+/K+-pump maintains the physiological K+ and Na+ electrochemical gradients across the cell membrane. It operates via an 'alternating-access' mechanism, making iterative transitions between inward-facing (E1) and outward-facing (E2) conformations. Although the general features of the...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-08-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/16616 |
| _version_ | 1811181456102260736 |
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| author | Huan Rui Pablo Artigas Benoît Roux |
| author_facet | Huan Rui Pablo Artigas Benoît Roux |
| author_sort | Huan Rui |
| collection | DOAJ |
| description | The Na+/K+-pump maintains the physiological K+ and Na+ electrochemical gradients across the cell membrane. It operates via an 'alternating-access' mechanism, making iterative transitions between inward-facing (E1) and outward-facing (E2) conformations. Although the general features of the transport cycle are known, the detailed physicochemical factors governing the binding site selectivity remain mysterious. Free energy molecular dynamics simulations show that the ion binding sites switch their binding specificity in E1 and E2. This is accompanied by small structural arrangements and changes in protonation states of the coordinating residues. Additional computations on structural models of the intermediate states along the conformational transition pathway reveal that the free energy barrier toward the occlusion step is considerably increased when the wrong type of ion is loaded into the binding pocket, prohibiting the pump cycle from proceeding forward. This self-correcting mechanism strengthens the overall transport selectivity and protects the stoichiometry of the pump cycle. |
| first_indexed | 2024-04-11T09:18:02Z |
| format | Article |
| id | doaj.art-5e19ee2ce6484533b9e5acc610af408e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:18:02Z |
| publishDate | 2016-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5e19ee2ce6484533b9e5acc610af408e2022-12-22T04:32:17ZengeLife Sciences Publications LtdeLife2050-084X2016-08-01510.7554/eLife.16616The selectivity of the Na+/K+-pump is controlled by binding site protonation and self-correcting occlusionHuan Rui0https://orcid.org/0000-0002-6459-9871Pablo Artigas1Benoît Roux2https://orcid.org/0000-0002-5254-2712Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United StatesDepartment of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, United StatesDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United StatesThe Na+/K+-pump maintains the physiological K+ and Na+ electrochemical gradients across the cell membrane. It operates via an 'alternating-access' mechanism, making iterative transitions between inward-facing (E1) and outward-facing (E2) conformations. Although the general features of the transport cycle are known, the detailed physicochemical factors governing the binding site selectivity remain mysterious. Free energy molecular dynamics simulations show that the ion binding sites switch their binding specificity in E1 and E2. This is accompanied by small structural arrangements and changes in protonation states of the coordinating residues. Additional computations on structural models of the intermediate states along the conformational transition pathway reveal that the free energy barrier toward the occlusion step is considerably increased when the wrong type of ion is loaded into the binding pocket, prohibiting the pump cycle from proceeding forward. This self-correcting mechanism strengthens the overall transport selectivity and protects the stoichiometry of the pump cycle.https://elifesciences.org/articles/16616free energymolecular dynamicssimulationsconformational transitions |
| spellingShingle | Huan Rui Pablo Artigas Benoît Roux The selectivity of the Na+/K+-pump is controlled by binding site protonation and self-correcting occlusion eLife free energy molecular dynamics simulations conformational transitions |
| title | The selectivity of the Na+/K+-pump is controlled by binding site protonation and self-correcting occlusion |
| title_full | The selectivity of the Na+/K+-pump is controlled by binding site protonation and self-correcting occlusion |
| title_fullStr | The selectivity of the Na+/K+-pump is controlled by binding site protonation and self-correcting occlusion |
| title_full_unstemmed | The selectivity of the Na+/K+-pump is controlled by binding site protonation and self-correcting occlusion |
| title_short | The selectivity of the Na+/K+-pump is controlled by binding site protonation and self-correcting occlusion |
| title_sort | selectivity of the na k pump is controlled by binding site protonation and self correcting occlusion |
| topic | free energy molecular dynamics simulations conformational transitions |
| url | https://elifesciences.org/articles/16616 |
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