TY - JOUR
T1 - Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site
AU - Wahlgren, Weixiao Y.
AU - Dunevall, Elin
AU - North, Rachel A.
AU - Paz, Aviv
AU - Scalise, Mariafrancesca
AU - Bisignano, Paola
AU - Bengtsson-Palme, Johan
AU - Goyal, Parveen
AU - Claesson, Elin
AU - Caing-Carlsson, Rhawnie
AU - Andersson, Rebecka
AU - Beis, Konstantinos
AU - Nilsson, Ulf J.
AU - Farewell, Anne
AU - Pochini, Lorena
AU - Indiveri, Cesare
AU - Grabe, Michael
AU - Dobson, Renwick C.J.
AU - Abramson, Jeff
AU - Ramaswamy, S.
AU - Friemann, Rosmarie
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
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.
UR - https://www.scopus.com/pages/publications/85046396061
U2 - 10.1038/s41467-018-04045-7
DO - 10.1038/s41467-018-04045-7
M3 - Article
C2 - 29717135
AN - SCOPUS:85046396061
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1753
ER -