TY - JOUR T1 - Substrate-bound outward-open structure of a Na-coupled sialic acid symporter reveals a new Na site. JF - Nat Commun Y1 - 2018 A1 - Wahlgren, Weixiao Y A1 - Dunevall, Elin A1 - North, Rachel A A1 - Paz, Aviv A1 - Scalise, Mariafrancesca A1 - Bisignano, Paola A1 - Bengtsson-Palme, Johan A1 - Goyal, Parveen A1 - Claesson, Elin A1 - Caing-Carlsson, Rhawnie A1 - Andersson, Rebecka A1 - Beis, Konstantinos A1 - Nilsson, Ulf J A1 - Farewell, Anne A1 - Pochini, Lorena A1 - Indiveri, Cesare A1 - Grabe, Michael A1 - Dobson, Renwick C J A1 - Abramson, Jeff A1 - Ramaswamy, S A1 - Friemann, Rosmarie AB -

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.

VL - 9 IS - 1 ER -