Research Article: The crystal structure of the TonB-dependent transporter YncD reveals a positively charged substrate-binding site

Date Published: May 01, 2020

Publisher: International Union of Crystallography

Author(s): Rhys Grinter, Trevor Lithgow.

http://doi.org/10.1107/S2059798320004398

Abstract

In this work, the structure and the phylogenetic distribution of the outer-membrane transporter YncD are determined, showing that YncD is unlikely to transport an iron-containing substrate.

Partial Text

The outer membrane of Gram-negative bacteria represents a formidable permeability barrier to hydrophilic molecules of larger than ∼600 Da (van den Berg et al., 2015 ▸). Hydrophilic molecules smaller than this diffusion limit cross the outer membrane through proteins called porins, which can be either promiscuous or substrate-specific (Vergalli et al., 2019 ▸). To import molecules that are too large for diffusion through outer-membrane porins, bacteria employ a diverse family of membrane proteins termed TonB-dependent transporters (TBDTs; Noinaj et al., 2010 ▸). These transporters in the outer membrane are so named because they engage in active transport, the energy for which is provided by the TonB–ExbBD complex in the inner membrane, which spans the periplasm to interact with TBDTs (Maki-Yonekura et al., 2018 ▸; Celia et al., 2016 ▸). TBDTs are specific for a particular substrate, which they bind with high affinity in an extracellular binding pocket (Grinter & Lithgow, 2019a ▸,b ▸). This high-affinity binding allows TBDTs to capture molecules that are of low abundance in the environment, enabling bacteria to scavenge scarce nutrients (Grinter & Lithgow, 2019a ▸). One such scarce nutrient is iron, which is the substrate of the majority of characterized TBDTs (Noinaj et al., 2010 ▸). Most iron-transporting TBDTs bind Fe3+ ions in complex with siderophores, organic molecules that bind metal ions with high affinity and are secreted by the bacteria or by competitors from the microbial community (Chu et al., 2010 ▸). In addition to importing Fe–siderophore complexes, some TBDTs harvest iron directly from proteins (Grinter et al., 2016 ▸; Noinaj et al., 2012 ▸). These protein-binding TBDTs often target host proteins and are employed by pathogens to obtain iron during infections (Leduc et al., 2008 ▸; Cornelissen et al., 1998 ▸).

Determination of the function of proteins is one of the most challenging aspects of modern protein biochemistry. The expansion of genomic and metagenomic sequencing data has provided a wealth of protein sequences, most of which are only partially characterized or of completely unknown function. Despite its difficulty, determining the function of novel proteins is invaluable, as without a robust understanding of the functional capacity of the proteome of an organism it is difficult to accurately predict its metabolic capabilities, physiology or lifestyle.

The following reference is cited in the supporting information for this article: Crooks et al. (2004 ▸).

 

Source:

http://doi.org/10.1107/S2059798320004398

 

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