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Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer
The common human pathogen Salmonella enterica takes up citrate as a nutrient via the sodium symporter SeCitS. Uniquely, our 2.5 Å x-ray structure of the SeCitS dimer shows three different conformations of the active protomer. One protomer is in the outside-facing state. Two are in different inside-f...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718727/ https://www.ncbi.nlm.nih.gov/pubmed/26636752 http://dx.doi.org/10.7554/eLife.09375 |
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author | Wöhlert, David Grötzinger, Maria J Kühlbrandt, Werner Yildiz, Özkan |
author_facet | Wöhlert, David Grötzinger, Maria J Kühlbrandt, Werner Yildiz, Özkan |
author_sort | Wöhlert, David |
collection | PubMed |
description | The common human pathogen Salmonella enterica takes up citrate as a nutrient via the sodium symporter SeCitS. Uniquely, our 2.5 Å x-ray structure of the SeCitS dimer shows three different conformations of the active protomer. One protomer is in the outside-facing state. Two are in different inside-facing states. All three states resolve the substrates in their respective binding environments. Together with comprehensive functional studies on reconstituted proteoliposomes, the structures explain the transport mechanism in detail. Our results indicate a six-step process, with a rigid-body 31° rotation of a helix bundle that translocates the bound substrates by 16 Å across the membrane. Similar transport mechanisms may apply to a wide variety of related and unrelated secondary transporters, including important drug targets. DOI: http://dx.doi.org/10.7554/eLife.09375.001 |
format | Online Article Text |
id | pubmed-4718727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-47187272016-01-21 Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer Wöhlert, David Grötzinger, Maria J Kühlbrandt, Werner Yildiz, Özkan eLife Biochemistry The common human pathogen Salmonella enterica takes up citrate as a nutrient via the sodium symporter SeCitS. Uniquely, our 2.5 Å x-ray structure of the SeCitS dimer shows three different conformations of the active protomer. One protomer is in the outside-facing state. Two are in different inside-facing states. All three states resolve the substrates in their respective binding environments. Together with comprehensive functional studies on reconstituted proteoliposomes, the structures explain the transport mechanism in detail. Our results indicate a six-step process, with a rigid-body 31° rotation of a helix bundle that translocates the bound substrates by 16 Å across the membrane. Similar transport mechanisms may apply to a wide variety of related and unrelated secondary transporters, including important drug targets. DOI: http://dx.doi.org/10.7554/eLife.09375.001 eLife Sciences Publications, Ltd 2015-12-04 /pmc/articles/PMC4718727/ /pubmed/26636752 http://dx.doi.org/10.7554/eLife.09375 Text en © 2015, Wöhlert et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry Wöhlert, David Grötzinger, Maria J Kühlbrandt, Werner Yildiz, Özkan Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer |
title | Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer |
title_full | Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer |
title_fullStr | Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer |
title_full_unstemmed | Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer |
title_short | Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer |
title_sort | mechanism of na(+)-dependent citrate transport from the structure of an asymmetrical cits dimer |
topic | Biochemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718727/ https://www.ncbi.nlm.nih.gov/pubmed/26636752 http://dx.doi.org/10.7554/eLife.09375 |
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