Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis.

Infection, survival, and proliferation of pathogenic bacteria in humans depend on their capacity to impair host responses and acquire nutrients in a hostile environment. Among such nutrients is heme, a co-factor for oxygen storage, electron transport, photosynthesis, and redox biochemistry, which is...

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Autores principales:	Halina Wójtowicz, Tibisay Guevara, Cynthia Tallant, Mariusz Olczak, Aneta Sroka, Jan Potempa, Maria Solà, Teresa Olczak, F Xavier Gomis-Rüth
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5401babd099e4124bfdf956a81364648
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spelling	oai:doaj.org-article:5401babd099e4124bfdf956a813646482021-11-25T05:47:57ZUnique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis.1553-73661553-737410.1371/journal.ppat.1000419https://doaj.org/article/5401babd099e4124bfdf956a813646482009-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19424422/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Infection, survival, and proliferation of pathogenic bacteria in humans depend on their capacity to impair host responses and acquire nutrients in a hostile environment. Among such nutrients is heme, a co-factor for oxygen storage, electron transport, photosynthesis, and redox biochemistry, which is indispensable for life. Porphyromonas gingivalis is the major human bacterial pathogen responsible for severe periodontitis. It recruits heme through HmuY, which sequesters heme from host carriers and delivers it to its cognate outer-membrane transporter, the TonB-dependent receptor HmuR. Here we report that heme binding does not significantly affect the secondary structure of HmuY. The crystal structure of heme-bound HmuY reveals a new all-beta fold mimicking a right hand. The thumb and fingers pinch heme iron through two apical histidine residues, giving rise to highly symmetric octahedral iron co-ordination. The tetrameric quaternary arrangement of the protein found in the crystal structure is consistent with experiments in solution. It shows that thumbs and fingertips, and, by extension, the bound heme groups, are shielded from competing heme-binding proteins from the host. This may also facilitate heme transport to HmuR for internalization. HmuY, both in its apo- and in its heme-bound forms, is resistant to proteolytic digestion by trypsin and the major secreted proteases of P. gingivalis, gingipains K and R. It is also stable against thermal and chemical denaturation. In conclusion, these studies reveal novel molecular properties of HmuY that are consistent with its role as a putative virulence factor during bacterial infection.Halina WójtowiczTibisay GuevaraCynthia TallantMariusz OlczakAneta SrokaJan PotempaMaria SolàTeresa OlczakF Xavier Gomis-RüthPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 5, p e1000419 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Halina Wójtowicz Tibisay Guevara Cynthia Tallant Mariusz Olczak Aneta Sroka Jan Potempa Maria Solà Teresa Olczak F Xavier Gomis-Rüth Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis.
description	Infection, survival, and proliferation of pathogenic bacteria in humans depend on their capacity to impair host responses and acquire nutrients in a hostile environment. Among such nutrients is heme, a co-factor for oxygen storage, electron transport, photosynthesis, and redox biochemistry, which is indispensable for life. Porphyromonas gingivalis is the major human bacterial pathogen responsible for severe periodontitis. It recruits heme through HmuY, which sequesters heme from host carriers and delivers it to its cognate outer-membrane transporter, the TonB-dependent receptor HmuR. Here we report that heme binding does not significantly affect the secondary structure of HmuY. The crystal structure of heme-bound HmuY reveals a new all-beta fold mimicking a right hand. The thumb and fingers pinch heme iron through two apical histidine residues, giving rise to highly symmetric octahedral iron co-ordination. The tetrameric quaternary arrangement of the protein found in the crystal structure is consistent with experiments in solution. It shows that thumbs and fingertips, and, by extension, the bound heme groups, are shielded from competing heme-binding proteins from the host. This may also facilitate heme transport to HmuR for internalization. HmuY, both in its apo- and in its heme-bound forms, is resistant to proteolytic digestion by trypsin and the major secreted proteases of P. gingivalis, gingipains K and R. It is also stable against thermal and chemical denaturation. In conclusion, these studies reveal novel molecular properties of HmuY that are consistent with its role as a putative virulence factor during bacterial infection.
format	article
author	Halina Wójtowicz Tibisay Guevara Cynthia Tallant Mariusz Olczak Aneta Sroka Jan Potempa Maria Solà Teresa Olczak F Xavier Gomis-Rüth
author_facet	Halina Wójtowicz Tibisay Guevara Cynthia Tallant Mariusz Olczak Aneta Sroka Jan Potempa Maria Solà Teresa Olczak F Xavier Gomis-Rüth
author_sort	Halina Wójtowicz
title	Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis.
title_short	Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis.
title_full	Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis.
title_fullStr	Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis.
title_full_unstemmed	Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis.
title_sort	unique structure and stability of hmuy, a novel heme-binding protein of porphyromonas gingivalis.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/5401babd099e4124bfdf956a81364648
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Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis.

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