Sialic acids are a large group of nine-carbon amino sugars that are widely distributed among mammals and higher metazoans. They are usually found conjugated to exterior cell surfaces. Commensal and pathogenic bacteria that colonise heavily sialylated niches (e.g., the mammalian respiratory tract and gut) can scavenge sialic acid from their surrounding environment and use it as a carbon, nitrogen and energy source—that is, they eat your glycoconjugates for breakfast. Sequestration and degradation of sialic acid involves specific amino sugar transporters responsible for the import into the bacterial cell and five catabolic enzymes that successively degrade sialic acid. Sialic acid utilization is essential for a range of human pathogenic bacteria. In this talk I will present our work that defines at the molecular level how TRipartite ATP-independent Periplasmic (TRAP) transporters import sialic acids in bacteria.
TRAP transporters that import sialic acids have two components: a soluble metabolite-scavenging protein (SiaP) and a membrane transport protein embedded in the cell membrane that comprises two subunits (SiaQ and SiaM). I will report the cryo-EM structures of several sialic acid TRAP transporters at 3 Å resolution or better. Rather than a monomer, we find that some TRAP transporter are homodimers. We observe lipids at the dimer interface, as well as a lipid trapped within the fusion that links the SiaQ and SiaM subunits. We show that the affinity (KD) for the complex between the soluble SiaP protein and SiaQM in the membrane is in the micromolar range. This work provides key data that enhances our understanding of the ‘elevator-with-an-operator’ mechanism of TRAP transporters.