TonB-Dependent Transporters: Regulation, Structure, and Function

Abstract

TonB-dependent transporters (TBDTs) are bacterial outer membrane proteins that bind and transport ferric chelates called siderophores, as well as vitamin B12, nickel complexes, and carbohydrates. The transport process requires energy in the form of protonmotive force and a complex of three inner membrane proteins, TonB-ExbB-ExbD, to transduce this energy to the outer membrane. The siderophore substrates range in complexity from simple small molecules such as citrate to large proteins like serum transferrin and haemoglobin. Because iron uptake is vital for almost all bacteria, expression of TBDTs is regulated in a number of ways that include metal-dependent regulators, σ/anti-σ factor systems, small RNAs, and even a riboswitch. In recent years many new structures of TBDTs have been solved in various states, resulting in a more complete picture of siderophore selectivity and binding, signal transduction across the outer membrane, and interaction with TonB-ExbB-ExbD. However, the transport mechanism is still unclear. In this review, we summarize recent progress in understanding regulation, structure and function in TBDTs and questions remaining to be answered.

New insights into iron acquisition by cyanobacteria: an essential role for ExbB-ExbD complex in inorganic iron uptake

“…Low sequence similarity show that this ExbB-ExbD-mediated iron uptake strategy is probably prevalent among most cyanobacteria species. The Ton transport system has been investigated for over 30 years in non-photosynthetic bacteria, and it is generally thought to be involved in transport of organic compounds such as Fe chelators, as the compounds are too large to pass through porins (Noinaj et al, 2010). For the first time, we have shown that the ExbB-ExbD-dependent transport system has an essential role in inorganic iron uptake in cyanobacteria.…”

“…TonB-ExbB-ExbD-dependent OM transporters are thought to be involved in uptake of organically chelated iron, such as siderophore-iron (Noinaj et al, 2010). To our knowledge, the involvement of this transport system in Fe 0 uptake has not been experimentally verified.…”

“…Unlike other organisms, Gram-negative bacteria possess an outer membrane (OM) as well as a cytoplasmic membrane (CM), which presents an additional barrier to the exchange of solutes. As ferri-siderophores are too large to passively diffuse through the OM porins, they must be actively transported across the membrane by specific receptor proteins (Miethke and Marahiel, 2007;Noinaj et al, 2010). The OM receptors/ transporters bind the ferri-siderophore complexes and directly interact with the energizing TonBExbB-ExbD complex in the inner membrane to allow the iron complex to be transported into the periplasmic space.…”

“…The OM receptors/ transporters bind the ferri-siderophore complexes and directly interact with the energizing TonBExbB-ExbD complex in the inner membrane to allow the iron complex to be transported into the periplasmic space. This transport process involves three components: (i) OM localized transporters; (ii) a CM-localized TonB-ExbB-ExbD complex, and (iii) ion electrochemical potential (Noinaj et al, 2010). Over the past three decades, many aspects of this TonB-ExbB-ExbD-dependent transport system have been revealed.…”

“…However, with regard to the substrates of the transport system, we are probably only seeing the 'tip of the iceberg' (Schauer et al, 2008). Originally, iron complexes and vitamin B 12 were thought to be the main substrates of the TonB-ExbB-ExbD system, but more and more new substrates have been found to be transported, including citrate, transferrin, hemoproteins, heme, phages, colicins, maltodextrins, nickel chelators and sucrose (Schauer et al, 2008;Noinaj et al, 2010).…”