Hijacking transferrin bound iron: protein–receptor interactions involved in iron transport in N. gonorrhoeae

Abstract

Neisseria gonorrhoeae has the capacity to acquire iron from its human host by removing this essential nutrient from serum transferrin. The transferrin binding proteins, TbpA and TbpB constitute the outer membrane receptor complex responsible for binding transferrin, extracting the tightly bound iron from the host-derived molecule, and transporting iron into the periplasmic space of this Gram-negative bacterium. Once iron is transported across the outer membrane, ferric binding protein A (FbpA) moves the iron across the periplasmic space and initiates the process of transport into the bacterial cytosol. The results of the studies reported here define the multiple steps in the iron transport process in which TbpA and TbpB participate. Using the SUPREX technique for assessing the thermodynamic stability of protein-ligand complexes, we report herein the first direct measurement of periplasmic FbpA binding to the outer membrane protein TbpA. We also show that TbpA discriminates between apo- and holo-FbpA; i.e. the TbpA interaction with apo-FbpA is higher affinity than the TbpA interaction with holo-FbpA. Further, we demonstrate that both TbpA and TbpB individually can deferrate transferrin and ferrate FbpA without energy supplied from TonB.

Evidence of Fe3+ interaction with the plug domain of the outer membrane transferrin receptor protein of Neisseria gonorrhoeae: implications for Fe transport

“…10 which shows a cascade of events whereby Fe 3+ is handed off from the cell exterior to the periplasm such that it is never present as “naked” or unchelated iron. The strong affinity of Tf for Fe 3+ is diminished by docking at the exterior surface of TbpA, presumably via a conformational change, 45 releasing the Fe 3+ to the β-barrel interior. The Fe 3+ then moves through the barrel weakly bound to the EIEYE sequence of the plug.…”

“…Fe 3+ is strongly bound to FbpA, which is a part of the periplasmic ABC transport system that delivers iron to the cytosol. 45 …”

“…1). 27,45,46 Although the energy requirement of each step described above is not clearly established, it has been shown by our laboratories in earlier reports that iron removal from holo-Tf by TbpA/TbpB is not TonB energy dependent, whereas removal of apo-transferrin from TbpA requires TonB energy. 27,45,46 …”

Structure of the bacterial plant-ferredoxin receptor FusA

“…This situation is even more pronounced for bacterial phytopathogens, where very little is known about the role that specific iron import systems play in infection1. The discovery of FusA demonstrates that, like their mammalian pathogenic counterparts, phytopathogenic bacteria can use a TBDR to specifically target iron-containing host proteins23. The presence of the FusA in Dickeya and Pantoea , which are closely related to Pectobacterium , suggests the ferredoxin uptake system represents an important iron acquisition tool for soft rot pathogens16.…”

Transition metals at the host–pathogen interface: howNeisseriaexploit human metalloproteins for acquiring iron and zinc

“…Following transport across the OM and entry into the periplasm, FbpA ( F e- b inding p rotein, a PBP) coordinates the Fe(III) ion and delivers it to the ABC transporter FbpBC for cytosolic delivery (Figure 2) [58,59]. FbpA is described as “bacterial transferrin” because of its structural and functional similarities with hTF [60].…”