Structural basis for iron piracy by pathogenic Neisseria

Nicholas Noinaj, et al. Nature. 483: 53-58, 2012.

Speaker: Yong-Shiang Cao(曹詠翔)                     Time: 13:00~14:00, April. 17, 2013

Commentator: Dr. Wen-Yih Jeng (鄭文義 老師) Place: Room 601

Abstract

Neisseria are one of the most causative human pathogens that invade the urogenital tract and nasopharynx, causing gonorrhoea, meningitis and other systemic infections. The Neisseria have been reported to uptake iron for survival and virulence¹. However, free iron is rare in the human body, generally being complexed by a number of high-affinity binding proteins. Neisseria extract iron directly from transferrin (TF) in the serum. TF-binding protein A (TbpA) and TF-binding protein B (TbpB) are the major proteins of Neisseria to obtain iron from TF². In this paper the authors aimed to answer two fundamental of how the human transferring (hTF) is specifically targeted, and of how the bacteria liberate iron from transferring? This study combined X-ray crystallography, small-angle X-ray scattering and electron microscopy to determine a model of the TbpA-TbpB-hTF iron import complex structure. The structure reveals that a large TbpA–hTF binding interface with many hTF-specific interactions, providing a rational basis for specificity. Iron releasing from the hTF by insertion to a helical element from TbpA into the iron-binding cleft and it transport across the outer membrane by TonB-dependent conformational changes in the TbpA plug domain. This study elucidates an important issue on iron transportation through membrane transporter TbpA-TbpB-hTF and provides the useful information for structure-based vaccine and drug design.

References

1.      Grifantini R, et al. (2003) Identification of iron-activated and -repressed Fur-dependent genes by transcriptome analysis of Neisseria meningitidis group B. Proceedings of the National Academy of Sciences of the United States of America 100(16):9542-9547.

2.      Krell T, et al. (2003) Insight into the structure and function of the transferrin receptor from Neisseria meningitidis using microcalorimetric techniques. The Journal of biological chemistry 278(17):14712-14722.