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Structural basis for haem piracy from host haemopexin by Haemophilus influenzae

Author

Listed:
  • Silvia Zambolin

    (CNRS, Université Paris 7 UMR 7099, Institut de Biologie Physico-Chimique)

  • Bernard Clantin

    (Université de Lille, CNRS, UMR 8576 - UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, Laboratoire de Biologie Structurale Intégrative)

  • Mohamed Chami

    (Center for Cellular Imaging and Nano Analytics (C-CINA), Biozentrum, University of Basel)

  • Sylviane Hoos

    (Institut Pasteur, Plate-forme de Biophysique, CNRS-UMR 3528)

  • Ahmed Haouz

    (Institut Pasteur, Plate-forme de Cristallographie, CNRS-UMR 3528, 25)

  • Vincent Villeret

    (Université de Lille, CNRS, UMR 8576 - UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, Laboratoire de Biologie Structurale Intégrative)

  • Philippe Delepelaire

    (CNRS, Université Paris 7 UMR 7099, Institut de Biologie Physico-Chimique)

Abstract

Haemophilus influenzae is an obligate human commensal/pathogen that requires haem for survival and can acquire it from several host haemoproteins, including haemopexin. The haem transport system from haem-haemopexin consists of HxuC, a haem receptor, and the two-partner-secretion system HxuB/HxuA. HxuA, which is exposed at the cell surface, is strictly required for haem acquisition from haemopexin. HxuA forms complexes with haem-haemopexin, leading to haem release and its capture by HxuC. The key question is how HxuA liberates haem from haemopexin. Here, we solve crystal structures of HxuA alone, and HxuA in complex with the N-terminal domain of haemopexin. A rational basis for the release of haem from haem-haemopexin is derived from both in vivo and in vitro studies. HxuA acts as a wedge that destabilizes the two-domains structure of haemopexin with a mobile loop on HxuA that favours haem ejection by redirecting key residues in the haem-binding pocket of haemopexin.

Suggested Citation

  • Silvia Zambolin & Bernard Clantin & Mohamed Chami & Sylviane Hoos & Ahmed Haouz & Vincent Villeret & Philippe Delepelaire, 2016. "Structural basis for haem piracy from host haemopexin by Haemophilus influenzae," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11590
    DOI: 10.1038/ncomms11590
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