The Sodium Sialic Acid Symporter From Staphylococcus aureus Has Altered Substrate Specificity

Frontiers in Chemistry
Rachel A NorthRenwick C J Dobson

Abstract

Mammalian cell surfaces are decorated with complex glycoconjugates that terminate with negatively charged sialic acids. Commensal and pathogenic bacteria can use host-derived sialic acids for a competitive advantage, but require a functional sialic acid transporter to import the sugar into the cell. This work investigates the sodium sialic acid symporter (SiaT) from Staphylococcus aureus (SaSiaT). We demonstrate that SaSiaT rescues an Escherichia coli strain lacking its endogenous sialic acid transporter when grown on the sialic acids N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc). We then develop an expression, purification and detergent solubilization system for SaSiaT and demonstrate that the protein is largely monodisperse in solution with a stable monomeric oligomeric state. Binding studies reveal that SaSiaT has a higher affinity for Neu5Gc over Neu5Ac, which was unexpected and is not seen in another SiaT homolog. We develop a homology model and use comparative sequence analyses to identify substitutions in the substrate-binding site of SaSiaT that may explain the altered specificity. SaSiaT is shown to be electrogenic, and transport is dependent upon more than one Na+ ion for every sialic acid mol...Continue Reading

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Citations

Jan 18, 2020·The Journal of Biological Chemistry·David CoombesRenwick C J Dobson
Jul 17, 2020·The Journal of Biological Chemistry·Andrew BellNathalie Juge
Nov 22, 2020·European Biophysics Journal : EBJ·Christopher R HorneRenwick C J Dobson
Mar 7, 2021·International Journal of Molecular Sciences·Tania HenriquezHeinrich Jung
Aug 27, 2021·The Journal of Biological Chemistry·Michael J CurrieRenwick C J Dobson

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Datasets Mentioned

BETA
AJ938182.1

Methods Mentioned

BETA
PCR
isothermal titration calorimetry
Size
microscale thermophoresis
size exclusion chromatography
Size-exclusion chromatography
microscale

Software Mentioned

SEDNTERP
ClustalW
EMBOSS stretcher
MEDELLER
NT Analysis
UltraScan
COOT
VMD MultiSeq
Grafit
GROMACS

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