Structural basis for iron piracy by pathogenic Neisseria

摘要

Neisseria are obligate human pathogens causing bacterial meningitis, septicaemia and gonorrhoea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co-receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are how human transferrin is specifically targeted, and how the bacteria liberate iron from transferrin at neutral pH. To address these questions, we solved crystal structures of the TbpA-transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB-transferrin complex by small-angle X-ray scattering and the TbpA-TbpB-transferrin complex by electron microscopy. Our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process.%致病性细菌利用-系列策略来在感染过程中从rn它们宿主获得铁。包括脑膜炎、败血症和淋病rn病原体在内的“奈瑟氏菌”，表达一种外膜蛋白rnTbpA和一种受体蛋白TbpB，二者一起能够直rn接从人的“铁传递蛋白”获取铁，促进铁的吸rn收。现在，研究人员通过结构分析揭示了铁获rn取机制。该结构对于基于结构的药物和疫苗设rn计工作会有用。