Journal article
Substrate-bound outward-open structure of a Na -coupled sialic acid symporter reveals a new Na site
Weixiao Y Wahlgren, Elin Dunevall, Rachel A North, Aviv Paz, Mariafrancesca Scalise, Paola Bisignano, Johan Bengtsson-Palme, Parveen Goyal, Elin Claesson, Rhawnie Caing-Carlsson, Rebecka Andersson, Konstantinos Beis, Ulf J Nilsson, Anne Farewell, Lorena Pochini, Cesare Indiveri, Michael Grabe, Renwick CJ Dobson, Jeff Abramson, S Ramaswamy Show all
NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2018
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+..
View full abstractGrants
Awarded by European Union's Seventh Framework Programme for research, technological development and demonstration
Awarded by Swedish Research Council
Awarded by Swedish Research Council Formas
Awarded by Swedish Governmental Agency for Innovation Systems (VINNOVA)
Awarded by Carl Tryggers Stiftelse for Vetenskaplig Forskning
Awarded by EMBO
Awarded by Magnus Bergvalls Stiftelse
Awarded by Italian Ministry of Instruction University and Research
Awarded by Wellcome Trust/DBT India Alliance Fellowship
Awarded by National Institutes of Health, NIH
Awarded by Indo-Swedish grant - Department of Biotechnology
Awarded by Royal Society of New Zealand Marsden Fund
Awarded by Biotechnology and Biological Sciences, Research Council
Awarded by Medical Research Council
Awarded by Wellcome Trust
Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
Funding Acknowledgements
We thank James Foadi for support with BLEND, Greger Hammarin, Jennie Sjohamn, Michael Jarva and Jonathan Herrmann for helpful discussions during the course of this work. We thank the Diamond Light Source and the Advanced Light Source for beam time allocation and access. The authors would like to acknowledge support of the Drug Discovery and Development Platform at Science for Life Laboratory, Sweden. The project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 608743 (to R.F.). This work was also supported by grants from the Swedish Research Council (2011-5790 to R.F.), the Swedish Research Council Formas (2010-1759 to R.F. and 221-2013-730 to W.Y.W.), the Swedish Governmental Agency for Innovation Systems (VINNOVA) (2013-04655 and 2017-00180 to R.F.), Carl Tryggers Stiftelse for Vetenskaplig Forskning (11:147 to R.F.), EMBO (1163-2014 to P.G. and 584-2014 to R.A.N.), Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg (to A.F., J.B.P. and R.F.), Magnus Bergvalls Stiftelse (2014-00536, 2015-00763, 2016-01606 to W.Y.W), the Italian Ministry of Instruction University and Research (PON01_ 00937 to C.I.), Wellcome Trust/DBT India Alliance Fellowship (IA/E/16/1/502999 to P.G.), National Institutes of Health, NIH (R01GM078844 to J.A. and R01GM089740 to M.G.), Indo-Swedish grant awarded by the Department of Biotechnology (BT/IN/Sweden/41/SR/2013 to S.R.), the Royal Society of New Zealand Marsden Fund (UOC1506 to R.C.J.D. and R.A.N.), Biomolecular Interaction Centre seed funding (to R.C.J.D. and R.A.N.), the Biotechnology and Biological Sciences, Research Council (BB/H01778X/1 to K.B.), the Medical Research Council (MR/N02103/1 to K.B.) and Wellcome Trust (MPL: WT/099165/Z/12/Z to S. Iwata).