Titre :

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

Auteur(s) :

Lebrun, Pierre [Auteur]
Université Lille Nord de France (COMUE)
Institut Pasteur de Lille
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Raze, Dominique [Auteur]
Université Lille Nord de France (COMUE)
Institut Pasteur de Lille
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Fritzinger, Bernd [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Université Lille Nord de France (COMUE)
Wieruszeski, Jean-Michel [Auteur]
Université Lille Nord de France (COMUE)
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Biet, Franck [Auteur]
Infectiologie et Santé Publique [UMR ISP]
Dose, Alexander [Auteur]
Carpentier, Mathieu [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Université Lille Nord de France (COMUE)
Schwarzer, Dirk [Auteur]
Allain, Fabrice [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Université Lille Nord de France (COMUE)
Lippens, Guy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Université Lille Nord de France (COMUE)
Locht, Camille [Auteur]
Université Lille Nord de France (COMUE)
Institut Pasteur de Lille
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]

Titre de la revue :

PLOS ONE

Pagination :

e32421

Éditeur :

Public Library of Science

Date de publication :

2012

ISSN :

1932-6203

Mot(s)-clé(s) en anglais :

extracting meaningful information, sex pheromone, plant odour, moth , olfactory receptor neurons, Agrotis ipsilon , extraction d'information pertinente

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM]

Résumé en anglais : [en]

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 ...
Lire la suite >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.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL