Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer

Elife. 2015 Dec 4:4:e09375. doi: 10.7554/eLife.09375.


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.

Keywords: Na+ transport; biochemistry; biophysics; citrate transport; crystal structure; membrane protein; membrane transport; secondary transport; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Biological Transport
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Citric Acid / metabolism*
  • Crystallography, X-Ray
  • Models, Molecular
  • Protein Conformation
  • Protein Multimerization
  • Salmonella enterica / enzymology*
  • Salmonella enterica / metabolism
  • Sodium / metabolism*


  • Bacterial Proteins
  • Carrier Proteins
  • CitS protein, bacteria
  • Citric Acid
  • Sodium

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.