Differential contribution of the repeats to heparin binding of HBHA, a major adhesin of Mycobacterium tuberculosis

Autor: Dominique Raze, Fabrice Allain, Franck Biet, Alexander Dose, Guy Lippens, Pierre Lebrun, Dirk Schwarzer, Mathieu Carpentier, Bernd Fritzinger, Jean-Michel Wieruszeski, Camille Locht
Přispěvatelé: Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP), Université Lille Nord de France (COMUE), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Infectiologie animale, Santé Publique (IASP311), Institut National de la Recherche Agronomique (INRA), Interfaculty Institute for biochemistry, Eberhard Karls Universität Tübingen, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Landrieu, Isabelle, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Tours
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Bacterial Diseases
Glycoconjugate
extracting meaningful information
sex pheromone
plant odour
moth
olfactory receptor neurons
Agrotis ipsilon
extraction d'information pertinente
Oligosaccharides
Plasma protein binding
Biochemistry
mécanisme moléculaire
Pathogenesis
chemistry.chemical_classification
0303 health sciences
Multidisciplinary
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
3. Good health
facteur de virulence
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biomolecules [q-bio.BM]
Infectious Diseases
Thermodynamics
Medicine
Research Article
Protein Binding
Repetitive Sequences
Amino Acid
Tuberculosis
[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
Science
Molecular Sequence Data
Biophysics
Virulence
adhésine
Biology
Microbiology
Mycobacterium tuberculosis
03 medical and health sciences
Bacterial Proteins
Species Specificity
medicine
Amino Acid Sequence
Adhesins
Bacterial
030304 developmental biology
Heparin
030306 microbiology
Proteins
Membrane Proteins
biology.organism_classification
medicine.disease
Protein Structure
Tertiary
Molecular Weight
Bacterial adhesin
chemistry
Membrane protein
Zdroj: PLoS ONE
PLoS ONE, Public Library of Science, 2012, 7 (3), pp.e32421. ⟨10.1371/journal.pone.0032421⟩
PLoS ONE, 2012, 7 (3), pp.e32421. ⟨10.1371/journal.pone.0032421⟩
PLoS ONE, Vol 7, Iss 3, p e32421 (2012)
Plos One 3 (7), . (2012)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0032421⟩
Popis: International audience; BACKGROUND: Tuberculosis remains one of the most important causes of global mortality and morbidity, and the molecular mechanisms of the pathogenesis are still incompletely understood. Only few virulence factors of the causative agent Mycobacterium tuberculosis are known. One of them is the heparin-binding haemagglutinin (HBHA), an important adhesin for epithelial cells and an extrapulmonary dissemination factor. HBHA mediates mycobacterial adherence to epithelial cells via the interactions of its C-terminal, lysine rich repeat domain with sulfated glycoconjugates on the surface of epithelial cells. METHODOLOGY/PRINCIPAL FINDINGS: Using defined heparin sulfate (HS) analogs, we determined the minimal heparin fragment length for HBHA binding and structural adaptations of the HBHA heparin-binding domain (HBD) upon binding to heparin. The NMR studies show significant shifts of all residues in the HBD upon interaction with heparin, with stronger shifts in the last repeats compared to the upstream repeats, and indicated that the HS fragments with 14 sugar units cover the entire C-terminal lysine-rich domain of HBHA. The differential implication of the repeats is determined by the relative position of prolines and lysines within each repeat, and may contribute to binding specificity. GAG binding induces a non-homogeneous structural rearrangement in the HBD, with stabilization of a nascent α-helix only in the last penta-repeats. CONCLUSION/SIGNIFICANCE: Mycobacterial HBHA undergoes structural adaptation upon interaction with GAGs, which is likely involved in binding specificities of the adhesin, and mycobacterial pathogens may use HBD polymorphisms for host or organ specificity. Further studies will aim at decoding the complementarity between HBD repeats and HS sequence.
Databáze: OpenAIRE
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