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

• Published in: Nature communications Vol. 9; no. 1; pp. 1753 - 14
• Main Authors: Wahlgren, Weixiao Y, Dunevall, Elin, North, Rachel A, Paz, Aviv, Scalise, Mariafrancesca, Bisignano, Paola, Bengtsson-Palme, Johan, Goyal, Parveen, Claesson, Elin, Caing-Carlsson, Rhawnie, Andersson, Rebecka, Beis, Konstantinos, Nilsson, Ulf J, Farewell, Anne, Pochini, Lorena, Indiveri, Cesare, Grabe, Michael, Dobson, Renwick C J, Abramson, Jeff, Ramaswamy, S, Friemann, Rosmarie
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.05.2018; Nature Publishing Group UK; Nature Portfolio
• Subjects: Acids; Amino Acid Sequence; Bacteria; Basic Medicine; Binding sites; Biochemistry and Molecular Biology; Biofysik; Biokemi och molekylärbiologi; Biophysics; Conformation; Energy consumption; Läkemedelskemi; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinal Chemistry; Medicinska och farmaceutiska grundvetenskaper; Microbiology in the medical area; Mikrobiologi inom det medicinska området; Molecular chains; Molecular dynamics; N-Acetylneuraminic acid; N-Acetylneuraminic Acid - metabolism; Organic Anion Transporters - chemistry; Organic Anion Transporters - metabolism; Protein Folding; Sequence Homology, Amino Acid; Sialic acids; Sodium; Sodium - metabolism; Structural Biology; Strukturbiologi; Substrate Specificity; Substrates; Symporters - chemistry; Symporters - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04045-7

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.