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

Biochem J. 2020 Jan 31;477(2):381-405. doi: 10.1042/BCJ20190607.


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 from 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 fulfill 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 modes. 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.

Keywords: HmuY; heme; hemophore; porphyromonas gingivalis; prevotella intermedia; protein structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Bacterial / genetics
  • Heme / chemistry
  • Heme / genetics*
  • Hemeproteins / chemistry
  • Hemeproteins / genetics*
  • Humans
  • Iron / metabolism
  • Periodontitis / genetics*
  • Periodontitis / microbiology
  • Periodontitis / pathology
  • Porphyromonas gingivalis / genetics
  • Porphyromonas gingivalis / pathogenicity
  • Prevotella intermedia / genetics*
  • Prevotella intermedia / pathogenicity
  • RNA, Messenger / genetics
  • Sequence Homology, Amino Acid


  • Hemeproteins
  • RNA, Messenger
  • Heme
  • Iron