Title :

Structural insights into a cooperative switch between one and two FimH bacterial adhesins binding pauci- and high-mannose type N-glycan receptors

Author(s) :

Krammer, Eva Maria [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Bridot, Clarisse [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Serna, Sonia [Auteur]
Basque Research and Technology Alliance [BRTA]
Echeverria, Begona [Auteur]
Basque Research and Technology Alliance [BRTA]
Semwal, Shubham [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Roubinet, Benoît [Auteur]
GLYcoDiag
van Noort, Kim [Auteur]
Wageningen University and Research [Wageningen] [WUR]
Wilbers, Ruud H. P. [Auteur]
Wageningen University and Research [Wageningen] [WUR]
Bourenkov, Gleb [Auteur]
European Molecular Biology Laboratory [Hamburg] [EMBL]
de Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Landemarre, Ludovic [Auteur]
GLYcoDiag
Niels, Reichardt [Auteur]
Centro Investigacion Biomedica en Red Bioingenieria, Biomateriales y Nanomedicina - CIBER-BBN (SPAIN)
Basque Research and Technology Alliance [BRTA]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Journal title :

Journal of Biological Chemistry

Abbreviated title :

J. Biol. Chem.

Volume number :

299

Pages :

104627

Publisher :

American Society for Biochemistry and Molecular Biology

Publication date :

2023-03-20

ISSN :

0021-9258

English keyword(s) :

FimH
N-glycan
multivalency
paucimannose
oligomannose-3
core fucose
oligomannose-6
kinetics
crystal structure
bacterial adhesion
cooperativity

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

The FimH type-1 fimbrial adhesin allows pathogenic Escherichia coli to adhere to glycoproteins in the epithelial linings of human bladder and intestinal tract, by using multiple fimbriae simultaneously. Pauci- and high-mannose ...
Show more >The FimH type-1 fimbrial adhesin allows pathogenic Escherichia coli to adhere to glycoproteins in the epithelial linings of human bladder and intestinal tract, by using multiple fimbriae simultaneously. Pauci- and high-mannose type N-glycans are natural FimH receptors on those glycoproteins. Oligomannose-3 and oligomannose-5 bind with the highest affinity to FimH by using the same Manα1,3Man branch. Oligomannose-6 is generated from oligomannose-5 in the next step of the biogenesis of high-mannose N-glycans, by the transfer of a mannose in α1,2-linkage onto this branch. Using serial crystallography and by measuring the kinetics of binding, we demonstrate that shielding the high-affinity epitope drives the binding of multiple FimH molecules. First, we profiled FimH glycan binding on a microarray containing paucimannosidic N-glycans and in a FimH LEctPROFILE assay. To make the transition to oligomannose-6, we measured the kinetics of FimH binding using paucimannosidic N-glycans, glycoproteins and all four α-dimannosides conjugated to bovine serum albumin. Equimolar mixed interfaces of the dimannosides present in oligomannose-6 and molecular dynamics simulations suggest a positive cooperativity in the bivalent binding of Manα1,3Manα1 and Manα1,6Manα1 dimannosides. The binding of core α1,6-fucosylated oligomannose-3 in cocrystals of FimH is monovalent but interestingly the GlcNAc1—Fuc moiety retains highly flexibility. In cocrystals with oligomannose-6, two FimH bacterial adhesins bind the Manα1,3Manα1 and Manα1,6Manα1 endings of the second trimannose core (A-4′-B). This cooperative switch towards bivalent binding appears sustainable beyond a molar excess of oligomannose-6. Our findings provide important novel structural insights for the design of multivalent FimH antagonists that bind with positive cooperativity.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

European Project :

Programme for EArly-stage Researchers in Lille

ANR Project :

Fonctionnalisations sélectives des tyrosines de protéines par électrochimie-click

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Computational Molecular Systems Biology

Submission date :

2023-08-01T18:45:09Z
2023-09-01T15:15:26Z