Titre :

A Novel Integrated Way for Deciphering the Glycan Code for the FimH Lectin

Auteur(s) :

Krammer, Eva-Maria [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Bilyy, Rostyslav [Auteur]
Blossey, Ralf [Auteur]
Centre National de la Recherche Scientifique [CNRS]
Szunerits, Sabine [Auteur]
NanoBioInterfaces - IEMN [NBI - IEMN]
Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 [IEMN]
Paryzhak, Solomiya [Auteur]
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Gouin, Sebastien [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Bridot, Clarisse [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Dumych, Tetiana [Auteur]

Titre de la revue :

Molecules

Pagination :

2794

Éditeur :

MDPI

Date de publication :

2018

ISSN :

1420-3049

Mot(s)-clé(s) en anglais :

FimH
binding mode
Enzyme-Linked LectinoSorbent assay
microcalorimetry
molecular dynamics
thermodynamics
entropy
high-mannose N-glycan

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Bactériologie

Résumé en anglais : [en]

The fimbrial lectin FimH from uro- and enteropathogenic Escherichia coli binds with nanomolar affinity to oligomannose glycans exposing Manα1,3Man dimannosides at their non-reducing end, but only with micromolar affinities ...
Lire la suite >The fimbrial lectin FimH from uro- and enteropathogenic Escherichia coli binds with nanomolar affinity to oligomannose glycans exposing Manα1,3Man dimannosides at their non-reducing end, but only with micromolar affinities to Manα1,2Man dimannosides. These two dimannoses play a significantly distinct role in infection by E. coli. Manα1,2Man has been described early on as shielding the (Manα1,3Man) glycan that is more relevant to strong bacterial adhesion and invasion. We quantified the binding of the two dimannoses (Manα1,2Man and Manα1,3Man to FimH using ELLSA and isothermal microcalorimetry and calculated probabilities of binding modes using molecular dynamics simulations. Our experimentally and computationally determined binding energies confirm a higher affinity of FimH towards the dimannose Manα1,3Man. Manα1,2Man displays a much lower binding enthalpy combined with a high entropic gain. Most remarkably, our molecular dynamics simulations indicate that Manα1,2Man cannot easily take its major conformer from water into the FimH binding site and that FimH is interacting with two very different conformers of Manα1,2Man that occupy 42% and 28% respectively of conformational space. The finding that Manα1,2Man binding to FimH is unstable agrees with the earlier suggestion that E. coli may use the Manα1,2Man epitope for transient tethering along cell surfaces in order to enhance dispersion of the infectionLire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Collections :

• Institut d'Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520

Source :

Harvested from HAL