<i>Tannerella</i> <i>forsythia</i> Tfo belongs to <i>Porphyromonas</i> <i>gingivalis</i> HmuY-like family of proteins but differs in heme-binding properties



Bielecki, Marcin, Antonyuk, Svetlana ORCID: 0000-0002-2779-9946, Strange, Richard W, Smalley, John W, Mackiewicz, Pawel, Smiga, Michal, Stepien, Paulina, Olczak, Mariusz and Olczak, Teresa
(2018) <i>Tannerella</i> <i>forsythia</i> Tfo belongs to <i>Porphyromonas</i> <i>gingivalis</i> HmuY-like family of proteins but differs in heme-binding properties. BIOSCIENCE REPORTS, 38 (5). BSR20181325-.

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Abstract

<i>Porphyromonas gingivalis</i> is considered the principal etiologic agent and keystone pathogen of chronic periodontitis. As an auxotrophic bacterium, it must acquire heme to survive and multiply at the infection site. <i>P. gingivalis</i> HmuY is the first member of a novel family of hemophore-like proteins. Bacterial heme-binding proteins usually use histidine-methionine or histidine-tyrosine residues to ligate heme-iron, whereas <i>P. gingivalis</i> HmuY uses two histidine residues. We hypothesized that other 'red complex' members, i.e. <i>Tannerella forsythia</i> and <i>Treponema denticola</i> might utilize similar heme uptake mechanisms to the <i>P. gingivalis</i> HmuY. Comparative and phylogenetic analyses suggested differentiation of HmuY homologs and low conservation of heme-coordinating histidine residues present in HmuY. The homologs were subjected to duplication before divergence of <i>Bacteroidetes</i> lineages, which could facilitate evolution of functional diversification. We found that <i>T. denticola</i> does not code an HmuY homolog. <i>T. forsythia</i> protein, termed as Tfo, binds heme, but preferentially in the ferrous form, and sequesters heme from the albumin-heme complex under reducing conditions. In agreement with that, the 3D structure of Tfo differs from that of HmuY in the folding of heme-binding pocket, containing two methionine residues instead of two histidine residues coordinating heme in HmuY. Heme binding to apo-HmuY is accompanied by movement of the loop carrying the His<sup>166</sup> residue, closing the heme-binding pocket. Molecular dynamics simulations (MD) demonstrated that this conformational change also occurs in Tfo. In conclusion, our findings suggest that HmuY-like family might comprise proteins subjected during evolution to significant diversification, resulting in different heme-binding properties.

Item Type: Article
Uncontrolled Keywords: Humans, Bacteroidetes, Porphyromonas gingivalis, Heme, Carrier Proteins, Hemeproteins, Phylogeny, Protein Conformation, Chronic Periodontitis, Molecular Dynamics Simulation, Tannerella forsythia, Heme-Binding Proteins
Depositing User: Symplectic Admin
Date Deposited: 28 Feb 2019 12:03
Last Modified: 13 Feb 2024 08:42
DOI: 10.1042/BSR20181325
Open Access URL: https://doi.org/10.1042/BSR20181325
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3033578