title: Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer.
abstract: 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.
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Wöhlert
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Grötzinger
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Kühlbrandt
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
authors.forename: Özkan
authors.identifier: http://orcid.org/0000-0003-3659-2805
authors.initials: Ö
authors.lastname: Yildiz
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D019343:Citric Acid / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D019779:Salmonella enterica / Q000201:enzymology* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C086246:CitS protein, bacteria; D019343:Citric Acid; D012964:Sodium
keywords: Na+ transport; biochemistry; biophysics; citrate transport; crystal structure; membrane protein; membrane transport; secondary transport; structural biology