The cysteine bond in the Escherichia coli FimH adhesin is critical for adhesion under flow conditions

Nilsson, LM, Yakovenko, O, Tchesnokova, V, Thomas, WE, Schembri, MA, Vogel, V, Klemm, P and Sokurenko, EV (2007) The cysteine bond in the Escherichia coli FimH adhesin is critical for adhesion under flow conditions. Molecular Microbiology, 65 5: 1158-1169. doi:10.1111/j.1365-2958.2007.05858.x


Author Nilsson, LM
Yakovenko, O
Tchesnokova, V
Thomas, WE
Schembri, MA
Vogel, V
Klemm, P
Sokurenko, EV
Title The cysteine bond in the Escherichia coli FimH adhesin is critical for adhesion under flow conditions
Formatted title
The cysteine bond in the Escherichia coli FimH adhesin is critical for adhesion under flow conditions
Journal name Molecular Microbiology   Check publisher's open access policy
ISSN 0950-382X
Publication date 2007-08-03
Sub-type Article (original research)
DOI 10.1111/j.1365-2958.2007.05858.x
Volume 65
Issue 5
Start page 1158
End page 1169
Total pages 12
Place of publication Oxford
Publisher Blackwell Publishing
Language eng
Subject 270301 Bacteriology
C1
730101 Infectious diseases
Abstract Cysteine bonds are found near the ligand-binding sites of a wide range of microbial adhesive proteins, including the FimH adhesin of Escherichia coli. We show here that removal of the cysteine bond in the mannose-binding domain of FimH did not affect FimH-mannose binding under static or low shear conditions (<= 0.2 dyne cm(-2)). However, the adhesion level was substantially decreased under increased fluid flow. Under intermediate shear (2 dynes cm(-2)), the ON-rate of bacterial attachment was significantly decreased for disulphide-free mutants. Molecular dynamics simulations demonstrated that the lower ON-rate of cysteine bond-free FimH could be due to destabilization of the mannose-free binding pocket of FimH. In contrast, mutant and wild-type FimH had similar conformation when bound to mannose, explaining their similar binding strength to mannose under intermediate shear. The stabilizing effect of mannose on disulphicle-free FimH was also confirmed by protection of the FimH from thermal and chemical inactivation in the presence of mannose. However, this stabilizing effect could not protect the integrity of FimH structure under high shear (> 20 dynes cm(-2)), where lack of the disulphide significantly increased adhesion OFF-rates. Thus, the cysteine bonds in bacterial adhesins could be adapted to enable bacteria to bind target surfaces under increased shear conditions.
Keyword Biochemistry & Molecular Biology
Microbiology
Molecular-dynamics
Bacterial Adhesion
Receptor-binding
Structural Basis
Water-molecules
Protein
Recognition
Force
Stability
Fimbriae
Q-Index Code C1
Q-Index Status Confirmed Code

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 17 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 19 Feb 2008, 00:58:18 EST