6OM5

Structure of a haemophore from Haemophilus haemolyticus

Summary for 6OM5

• Entry DOI: 10.2210/pdb6om5/pdb
• Descriptor: haemophore, PROTOPORPHYRIN IX CONTAINING FE, SULFATE ION, ... (6 entities in total)
• Functional Keywords: haemophilus haemolyticus, haemophore, antimicrobial, metal transport
• Biological source: Haemophilus haemolyticus M19107
• Total number of polymer chains: 1
• Total formula weight: 28744.75

Authors

Torrado, M.,Walshe, J.L.,Mackay, J.P.,Guss, J.M.,Gell, D.A. (deposition date: 2019-04-18, release date: 2019-12-04, Last modification date: 2024-03-13)

Primary citation

Latham, R.D.,Torrado, M.,Atto, B.,Walshe, J.L.,Wilson, R.,Guss, J.M.,Mackay, J.P.,Tristram, S.,Gell, D.A.
A heme-binding protein produced by Haemophilus haemolyticus inhibits non-typeable Haemophilus influenzae.
Mol.Microbiol., 113:381-398, 2020

PubMed Abstract: Commensal bacteria serve as an important line of defense against colonisation by opportunisitic pathogens, but the underlying molecular mechanisms remain poorly explored. Here, we show that strains of a commensal bacterium, Haemophilus haemolyticus, make hemophilin, a heme-binding protein that inhibits growth of the opportunistic pathogen, non-typeable Haemophilus influenzae (NTHi) in culture. We purified the NTHi-inhibitory protein from H. haemolyticus and identified the hemophilin gene using proteomics and a gene knockout. An x-ray crystal structure of recombinant hemophilin shows that the protein does not belong to any of the known heme-binding protein folds, suggesting that it evolved independently. Biochemical characterisation shows that heme can be captured in the ferrous or ferric state, and with a variety of small heme-ligands bound, suggesting that hemophilin could function under a range of physiological conditions. Hemophilin knockout bacteria show a limited capacity to utilise free heme for growth. Our data suggest that hemophilin is a hemophore and that inhibition of NTHi occurs by heme starvation, raising the possibility that competition from hemophilin-producing H. haemolyticus could antagonise NTHi colonisation in the respiratory tract.

PubMed: 31742788
DOI: 10.1111/mmi.14426

Experimental method

X-RAY DIFFRACTION (1.6 Å)