Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wöhlert, David, Grötzinger, Maria J, Kühlbrandt, Werner, Yildiz, Özkan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
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
_version_ 1782410848330842112
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
work_keys_str_mv AT wohlertdavid mechanismofnadependentcitratetransportfromthestructureofanasymmetricalcitsdimer
AT grotzingermariaj mechanismofnadependentcitratetransportfromthestructureofanasymmetricalcitsdimer
AT kuhlbrandtwerner mechanismofnadependentcitratetransportfromthestructureofanasymmetricalcitsdimer
AT yildizozkan mechanismofnadependentcitratetransportfromthestructureofanasymmetricalcitsdimer