Journal of Biological Chemistry
Volume 285, Issue 51, 17 December 2010, Pages 40028-40038
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Microbiology
Characterization of a Hemophore-like Protein from Porphyromonas gingivalis*

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The porphyrin auxotrophic pathogen Porphyromonas gingivalis obtains the majority of essential iron and porphyrin from host hemoproteins. To achieve this, the organism expresses outer membrane gingipains containing cysteine proteinase domains linked to hemagglutinin domains. Heme mobilized in this way is taken up by P. gingivalis through a variety of potential portals where HmuY/HmuR of the hmu locus are best described. These receptors have relatively low binding affinities for heme. In this report, we describe a novel P. gingivalis protein, HusA, the product of PG2227, which rapidly bound heme with a high binding constant at equilibrium of 7 × 10−10 m. HusA is both expressed on the outer membrane and released from the organism. Spectral analysis indicated an unusual pattern of binding where heme was ligated preferentially as a dimer. Further, the presence of dimeric heme induced protein dimer formation. Deletional inactivation of husA showed that expression of this moiety was essential for growth of P. gingivalis under conditions of heme limitation. This finding was in accord with the pronounced increase in gene expression levels for husA with progressive reduction of heme supplementation. Antibodies reactive against HusA were detected in patients with chronic periodontitis, suggesting that the protein is expressed during the course of infection by P. gingivalis. It is predicted that HusA efficiently sequesters heme from gingipains and fulfills the function of a high affinity hemophore-like protein to meet the heme requirement for growth of P. gingivalis during establishment of infection.

Bacteria
Bacterial Metabolism
Heme
Iron Metabolism
Spectroscopy
Hemophore
Porphyromonas gingivalis

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*

This work was supported by Grant LP0562660 from the Australian Research Council (to N. H.) and Establishment Grant RN38/08 from the Ramaciotti Foundation (to K.-A. N.).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables S1 and S2 and Figs. S1–S3.

1

Supported by Ph.D. scholarship from the New South Wales Dental Board, Australia and Bela Schwartz Foundation, and the University of Sydney.