The Streptococcus pyogenes Shr protein captures human hemoglobin using two structurally unique binding domains

摘要: In order to proliferate and mount an infection, many bacterial pathogens need acquire iron from their host. The most abundant source in the body is oxygen transporter hemoglobin (Hb). Streptococcus pyogenes, a potentially lethal human pathogen, uses Shr protein capture Hb on cell surface. important virulence factor, yet mechanism by which it captures acquires its heme not well-understood. Here, we show using NMR biochemical methods that binds two related modules were previously defined as domains of unknown function (DUF1533). These hemoglobin-interacting (HIDs), called HID1 HID2, are autonomously folded independently bind Hb. 1.5 A resolution crystal structure HID2 revealed structurally unique Hb-binding domain. Mutagenesis studies conserved tyrosine both HIDs essential for binding. Our indicate with higher affinity than tetramer engaged receptors. reveal presence third domain between heme-binding NEAT1 domain, suggesting this linker may position near capture.