Publication

Article Metrics

Citations


Online attention

Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site

DOI: 10.1038/s41467-018-04045-7 DOI Help

Authors: Weixiao Yuan Wahlgren (University of Gothenburg; Imperial College London; Diamond Light Source; Rutherford Appleton Laboratory) , Elin Dunevall (University of Gothenburg) , Rachel A. North (University of Gothenburg; University of Canterbury) , Aviv Paz (University of California) , Mariafrancesca Scalise (University of Calabria) , Paola Bisignano (University of California) , Johan Bengtsson-palme (University of Gothenburg) , Parveen Goyal (University of Gothenburg) , Elin Claesson (University of Gothenburg) , Rhawnie Caing-carlsson (University of Gothenburg) , Rebecka Andersson (University of Gothenburg) , Konstantinos Beis (Imperial College London; Diamond Light Source; Rutherford Appleton Laboratory) , Ulf J. Nilsson (Lund University) , Anne Farewell (University of Gothenburg) , Lorena Pochini (University of Calabria) , Cesare Indiveri (University of Calabria) , Michael Grabe (University of California) , Renwick C. J. Dobson (University of Canterbury; University of Melbourne) , Jeff Abramson (University of California; The Institute for Stem Cell Biology and Regenerative Medicine (InStem)) , Sneha Ramaswamy (The Institute for Stem Cell Biology and Regenerative Medicine (InStem)) , Rosmarie Friemann (University of Gothenburg; School of Medicine Stanford University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 9

State: Published (Approved)
Published: May 2018
Diamond Proposal Number(s): 11641

Open Access Open Access

Abstract: Many pathogenic bacteria utilise sialic acids as an energy source or use them as an external coating to evade immune detection. As such, bacteria that colonise sialylated environments deploy specific transporters to mediate import of scavenged sialic acids. Here, we report a substrate-bound 1.95 Å resolution structure and subsequent characterisation of SiaT, a sialic acid transporter from Proteus mirabilis. SiaT is a secondary active transporter of the sodium solute symporter (SSS) family, which use Na+ gradients to drive the uptake of extracellular substrates. SiaT adopts the LeuT-fold and is in an outward-open conformation in complex with the sialic acid N-acetylneuraminic acid and two Na+ ions. One Na+ binds to the conserved Na2 site, while the second Na+ binds to a new position, termed Na3, which is conserved in many SSS family members. Functional and molecular dynamics studies validate the substrate-binding site and demonstrate that both Na+ sites regulate N-acetylneuraminic acid transport.

Journal Keywords: Antimicrobials; Glycobiology; Medicinal chemistry; Molecular biophysics; X-ray crystallography

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I24-Microfocus Macromolecular Crystallography

Documents:
s41467-018-04045-7.pdf