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Prevotella intermedia produces two proteins homologous to Porphyromonas gingivalis HmuY but with different heme coordination mode

DOI: 10.1042/BCJ20190607 DOI Help

Authors: Marcin Bielecki (University of Wroclaw) , Svetlana Antonyuk (University of Liverpool) , Richard W. Strange (University of Essex) , Klaudia Siemińska (University of Wroclaw) , John W. Smalley (University of Liverpool) , Paweł Mackiewicz (University of Wroclaw) , Michał Śmiga (University of Wroclaw) , Megan Cowan (University of Essex) , Michael J. Capper (Icahn School of Medicine at Mount Sinai) , Paulina Ślęzak (University of Wroclaw) , Mariusz Olczak (University of Wroclaw) , Teresa Olczak (University of Wroclaw)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochemical Journal

State: Published (Approved)
Published: January 2020
Diamond Proposal Number(s): 15991

Open Access Open Access

Abstract: As part of the infective process, Porphyromonas gingivalis must acquire heme which is indispensable for life and enables the microorganism to survive and multiply at the infection site. This oral pathogenic bacterium uses a newly discovered novel hmu heme uptake system with a leading role played by the HmuY hemophore-like protein, responsible for acquiring heme and increasing virulence of this periodontopathogen. We demonstrated that Prevotella intermedia produces two HmuY homologs, termed PinO and PinA. Both proteins were produced at higher mRNA and protein levels when the bacterium grew under low-iron/heme conditions. PinO and PinA bound heme, but preferentially under reducing conditions, and in a manner different to that of the P. gingivalis HmuY. The analysis of the three-dimensional structures confirmed differences between apo-PinO and apo-HmuY, mainly in the fold forming the heme-binding pocket. Instead of two histidine residues coordinating heme iron in P. gingivalis HmuY, PinO and PinA could use one methionine residue to fulfil this function, with potential support of additional methionine residue/s. The P. intermedia proteins sequestered heme only from the host albumin-heme complex under reducing conditions. Our findings suggest that HmuY-like family might comprise proteins subjected during evolution to significant diversification, resulting in different heme coordination mode. The newer data presented in this manuscript on HmuY homologs produced by P. intermedia sheds more light on the novel mechanism of heme uptake, could be helpful in discovering their biological function, and in developing novel therapeutic approaches.

Journal Keywords: Porphyromonas gingivalis; Prevotella intermedia; heme; HmuY; hemophore; protein structure

Subject Areas: Biology and Bio-materials

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)


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