Oral Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Crystal structure of a sialic acid transporter (#31)

Weixiao Wahlgren 1 2 3 4 5 , Elin Dunevall 1 2 , Rachel North 1 6 , Aviv Paz 7 , Maria Francesca Scalise 8 , Paola Bisignano 9 , Parveen Goyal 1 2 , Elin Claesson 1 , Johan Bengtsson-Palme 2 10 , Rhawnie Caing Carlsson 1 , Rebecka Andersson 1 , Glareh Askarieh 11 , Konstantinos Beis 3 4 5 , Anne Farewell 1 2 , Renwick Dobson 6 12 , Lorena Pochini 8 , Michael Grabe 9 , Cesare Indiver 8 , Jeff Abramson 7 13 , S. Ramaswamy 13 , Rosmarie Friemann 1 2 14
  1. Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
  2. Centre for Antibiotic Resistance Research (CARe), University of Gothenburg, Gothenburg, Sweden
  3. Department of Life Sciences, Imperial College London, London, U.K.
  4. Membrane Protein Lab, Diamond Light Source, Chilton, Oxfordshire, U.K.
  5. Rutherford Appleton Laboratory, Research Complex at Harwell, Didcot, Oxfordshire, U.K.
  6. Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury, Christchurch, New Zealand
  7. Department of Physiology, Geffen School of Medicine, University of California, Los Angeles, CA, USA
  8. Department DiBEST Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Arcavacata di Rende, Italy
  9. Cardiovascular Research Institute, Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA
  10. Department of Infectious Diseases, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  11. Medivir AB, Huddinge, Sweden
  12. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia
  13. The institute for Stem Cell Biology and Regenerative Medicine (instem), National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, India
  14. Department of Structural Biology, School of Medicine Stanford University, Stanford, CA, USA

 

 

Sialic acids comprise a varied group of nine-carbon amino sugars widely distributed among mammals and higher metazoans. Commensal and pathogenic bacteria that colonise heavily sialiated niches (e.g. the mammalian respiratory tract and gut) can scavenge sialic acids from their surrounding environment. Scavenged sialic acid is used as a carbon, nitrogen and energy source, or to evade the host immune response by decorating their outer surfaces in sialic acid1,2.

Bacterial sialic acid specific membrane protein transport systems have been identified that belong to the tripartite ATP-independent periplasmic transporters, ATP-binding cassette, major facilitator superfamily and sodium solute symporter transport transport systems3-6.

Here we report the unpublished 1.95 Å resolution crystal structure of a sialic acid specific sodium solute symporter, SiaT, in its outward-open conformation. The structure of SiaT was determined in complex with sodium and sialic acid bound, providing insight into how this transporter mediates the movement of sialic acid across the membrane. The overall structure contains 13 transmembrane helices where the structural core is formed from two inverted repeats of five transmembrane helices each, as seen in other sodium symporters, including the galactose transporter (vSGLT), and leucine transporter (LeuT).

A sodium molecule occupies the cation-binding site equivalent to the Na2-site in LeuT-like fold transporters. A putative sodium site was also found at a previously proposed sodium escape pathway on the intracellular side. Structural and biochemical analyses elucidate essential transport residues and for the first time, a sialic acid transporter has been characterised. Molecular modeling and molecular dynamics simulations provide insight on the transport mechanism employed by SiaT.

 

 

 

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