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-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.

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Author:David Wöhlert, Maria J. Grötzinger, Werner KühlbrandtORCiDGND, Özkan YildizORCiDGND
Pubmed Id:
Parent Title (English):eLife
Publisher:eLife Sciences Publications
Place of publication:Cambridge
Document Type:Article
Date of Publication (online):2015/12/04
Date of first Publication:2015/12/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2016/08/23
Tag:Na+ transport; biochemistry; biophysics; citrate transport; crystal structure; membrane protein; membrane transport; secondary transport; structural biology
First Page:18
Copyright Wöhlert et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung 4.0