title: Structural basis for haem piracy from host haemopexin by Haemophilus influenzae.
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.
authors.affiliation: CNRS, Université Paris 7 UMR 7099, Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zambolin
authors.affiliation: Université de Lille, CNRS, UMR 8576 - UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, Laboratoire de Biologie Structurale Intégrative, F 59000 Lille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Clantin
authors.affiliation: Center for Cellular Imaging and Nano Analytics (C-CINA), Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chami
authors.affiliation: Institut Pasteur, Plate-forme de Biophysique, CNRS-UMR 3528, 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Hoos
authors.affiliation: Institut Pasteur, Plate-forme de Cristallographie, CNRS-UMR 3528, 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Haouz
authors.affiliation: Université de Lille, CNRS, UMR 8576 - UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, Laboratoire de Biologie Structurale Intégrative, F 59000 Lille, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Villeret
authors.affiliation: CNRS, Université Paris 7 UMR 7099, Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Philippe
authors.identifier: 0000-0002-5190-7118
authors.initials: P
authors.lastname: Delepelaire
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli; D006193:Haemophilus influenzae / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D011817:Rabbits; D018000:Receptors, Peptide / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: D001426:Bacterial Proteins; D018000:Receptors, Peptide; C047453:hemopexin receptor; D006418:Heme