Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS

Abstract The sodium-dependent citrate transporter of Klebsiella pneumoniae (KpCitS) belongs to the 2-hydroxycarboxylate transporter (2-HCT) family and allows the cell to use citrate as sole carbon and energy source in anaerobic conditions. Here we present crystal structures of KpCitS in citrate-boun...

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Autores principales:	Ji Won Kim, Subin Kim, Songwon Kim, Haerim Lee, Jie-Oh Lee, Mi Sun Jin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/784b69cee4a042e8be3b47f52c78fa74
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spelling	oai:doaj.org-article:784b69cee4a042e8be3b47f52c78fa742021-12-02T11:40:20ZStructural insights into the elevator-like mechanism of the sodium/citrate symporter CitS10.1038/s41598-017-02794-x2045-2322https://doaj.org/article/784b69cee4a042e8be3b47f52c78fa742017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02794-xhttps://doaj.org/toc/2045-2322Abstract The sodium-dependent citrate transporter of Klebsiella pneumoniae (KpCitS) belongs to the 2-hydroxycarboxylate transporter (2-HCT) family and allows the cell to use citrate as sole carbon and energy source in anaerobic conditions. Here we present crystal structures of KpCitS in citrate-bound outward-facing, citrate-bound asymmetric, and citrate-free inward-facing state. The structures reveal that the KpCitS dimerization domain remains stationary throughout the transport cycle due to a hydrogen bond network as well as extensive hydrophobic interactions. In contrast, its transport domain undergoes a ~35° rigid-body rotation and a ~17 Å translocation perpendicular to the membrane to expose the substrate-binding site alternately to either side of the membrane. Furthermore, homology models of two other 2-HCT proteins based on the KpCitS structure offer structural insights into their differences in substrate specificity at a molecular level. On the basis of our results and previous biochemical data, we propose that the activity of the 2-HCT CitS involves an elevator-like movement in which the transport domain itself traverses the lipid bilayer, carrying the substrate into the cell in a sodium-dependent manner.Ji Won KimSubin KimSongwon KimHaerim LeeJie-Oh LeeMi Sun JinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ji Won Kim Subin Kim Songwon Kim Haerim Lee Jie-Oh Lee Mi Sun Jin Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS
description	Abstract The sodium-dependent citrate transporter of Klebsiella pneumoniae (KpCitS) belongs to the 2-hydroxycarboxylate transporter (2-HCT) family and allows the cell to use citrate as sole carbon and energy source in anaerobic conditions. Here we present crystal structures of KpCitS in citrate-bound outward-facing, citrate-bound asymmetric, and citrate-free inward-facing state. The structures reveal that the KpCitS dimerization domain remains stationary throughout the transport cycle due to a hydrogen bond network as well as extensive hydrophobic interactions. In contrast, its transport domain undergoes a ~35° rigid-body rotation and a ~17 Å translocation perpendicular to the membrane to expose the substrate-binding site alternately to either side of the membrane. Furthermore, homology models of two other 2-HCT proteins based on the KpCitS structure offer structural insights into their differences in substrate specificity at a molecular level. On the basis of our results and previous biochemical data, we propose that the activity of the 2-HCT CitS involves an elevator-like movement in which the transport domain itself traverses the lipid bilayer, carrying the substrate into the cell in a sodium-dependent manner.
format	article
author	Ji Won Kim Subin Kim Songwon Kim Haerim Lee Jie-Oh Lee Mi Sun Jin
author_facet	Ji Won Kim Subin Kim Songwon Kim Haerim Lee Jie-Oh Lee Mi Sun Jin
author_sort	Ji Won Kim
title	Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS
title_short	Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS
title_full	Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS
title_fullStr	Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS
title_full_unstemmed	Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS
title_sort	structural insights into the elevator-like mechanism of the sodium/citrate symporter cits
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/784b69cee4a042e8be3b47f52c78fa74
work_keys_str_mv	AT jiwonkim structuralinsightsintotheelevatorlikemechanismofthesodiumcitratesymportercits AT subinkim structuralinsightsintotheelevatorlikemechanismofthesodiumcitratesymportercits AT songwonkim structuralinsightsintotheelevatorlikemechanismofthesodiumcitratesymportercits AT haerimlee structuralinsightsintotheelevatorlikemechanismofthesodiumcitratesymportercits AT jieohlee structuralinsightsintotheelevatorlikemechanismofthesodiumcitratesymportercits AT misunjin structuralinsightsintotheelevatorlikemechanismofthesodiumcitratesymportercits
_version_	1718395653348917248

Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS

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