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Conformational Switch of the Bacterial Adhesin FimH in the Absence of the Regulatory Domain: Engineering a Minimalistic Allosteric System
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4042135
Author(s) Rabbani, Said; Fiege, Brigitte; Eris, Deniz; Silbermann, Marleen; Jakob, Roman Peter; Navarra, Giulio; Maier, Timm; Ernst, Beat
Author(s) at UniBasel Maier, Timm
Ernst, Beat
Rabbani, Said
Navarra, Giulio
Jakob, Roman Peter
Fiege, Brigitte
Eris, Deniz
Silbermann, Marleen
Year 2018
Title Conformational Switch of the Bacterial Adhesin FimH in the Absence of the Regulatory Domain: Engineering a Minimalistic Allosteric System
Journal Journal of Biological Chemistry
Volume 293
Number 5
Pages / Article-Number 1835-1849
Keywords bacterial adhesion; circular dichroism (CD); isothermal titration calorimetry (ITC); nuclear magnetic resonance (NMR); surface plasmon resonance (SPR); chemical shift perturbation (CSP); fluorescence polarization (FP); full length (FL); lectin domain (LD); pilin domain (PD)
Abstract For many biological processes such as ligand binding, enzymatic catalysis, or protein folding, allosteric regulation of protein conformation and dynamics is fundamentally important. One example is the bacterial adhesin FimH, where the C-terminal pilin domain exerts negative allosteric control over binding of the N-terminal lectin domain to mannosylated ligands on host cells. When the lectin and pilin domains are separated under shear stress, the FimH-ligand interaction switches in a so-called catch-bond mechanism from low to high affinity state. So far, it has been assumed that the pilin domain is essential for the allosteric propagation within the lectin domain that would otherwise be conformationally rigid. To test this hypothesis, we generated mutants of the isolated FimH lectin domain and characterized their thermodynamic, kinetic, and structural properties using ITC, SPR, NMR and X-ray techniques. Intriguingly, some of the mutants mimicked the conformational and kinetic behaviors of the full-length protein and, even in absence of the pilin domain, conducted the crosstalk between allosteric sites and the mannoside binding pocket. Thus, these mutants represent a minimalistic allosteric system of FimH, useful for further mechanistic studies and antagonist design.
Publisher American Society for Biochemistry and Molecular Biology
ISSN/ISBN 0021-9258 ; 1083-351X
URL http://www.jbc.org/content/early/2017/11/27/jbc.M117.802942.abstract
edoc-URL http://edoc.unibas.ch/57369/
Full Text on edoc No
Digital Object Identifier DOI 10.1074/jbc.M117.802942
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/29180452
ISI-Number 000424201700032
Document type (ISI) Article
 
   

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29/03/2024