Crystal Structure of the Heme-IsdC Complex, the Central Conduit of the Isd Iron/Heme Uptake System in Staphylococcus aureus

摘要: Pathogens such as Staphylococcus aureus require iron to survive and have evolved specialized proteins steal heme from their host. IsdC is the central conduit of Isd (iron-regulated surface determinant) multicomponent uptake machinery; staphylococcal cell-surface IsdA, IsdB, IsdH are thought funnel molecular cargo IsdC, which then mediates transfer iron-containing nutrient membrane translocation system IsdDEF. The structure heme-IsdC complex reveals a novel site within an immunoglobulin-like domain sheds light on its binding mechanism. folding topology reminiscent architecture cytochrome f, cellobiose dehydrogenase, ethylbenzene dehydrogenase; in these three proteins, bound equivalent position, but interestingly, features distinct pocket with ligand located next hydrophobic core β-sandwich. coordinated tyrosine surrounded by several non-polar side chains that cluster into tightly packed proximal side. On other hand, distal relatively exposed short helical peptide segment acts lip clasping onto almost half porphyrin plane. This structural feature argued play role mechanism release switching open conformation thus loosening interactions holding heme. provides template for understanding IsdH, contain same heme-binding module known NEAT (near transporter) domain.