HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 12, 7823-7833, March 21, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/12/7823    most recent M707804200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tchesnokova, V. Articles by Sokurenko, E. Search for Related Content PubMed PubMed Citation Articles by Tchesnokova, V. Articles by Sokurenko, E. Social Bookmarking                      What's this?

Integrin-like Allosteric Properties of the Catch Bond-forming FimH Adhesin of Escherichia coli^*

Veronika Tchesnokova¹, Pavel Aprikian¹, Olga Yakovenko¹, Christopher LaRock, Brian Kidd, Viola Vogel^¶, Wendy Thomas^||2, and Evgeni Sokurenko^||3

From the Departments of Microbiology and Bioengineering and the ^||Nanotechnology Center, University of Washington, Seattle, Washington 98105 and the ^¶Department of Materials, ETH Zurich, 8093 Zurich, Switzerland

FimH is the adhesive subunit of type 1 fimbriae of the Escherichia coli that is composed of a mannose-binding lectin domain and a fimbria-incorporating pilin domain. FimH is able to interact with mannosylated surface via a shear-enhanced catch bond mechanism. We show that the FimH lectin domain possesses a ligand-induced binding site (LIBS), a type of allosterically regulated epitopes characterized in integrins. Analogous to integrins, in FimH the LIBS epitope becomes exposed in the presence of the ligand (or "activating" mutations) and is located far from the ligand-binding site, close to the interdomain interface. Also, the antibody binding to the LIBS shifts adhesin from the low to high affinity state. Binding of streptavidin to the biotinylated residue within the LIBS also locks FimH in the high affinity state, suggesting that the allosteric perturbations in FimH are sustained by the interdomain wedging. In the presence of antibodies, the strength of bacterial adhesion to mannose is increased similar to the increase observed under shear force, suggesting the same allosteric mechanism, a shift in the interdomain configuration. Thus, an integrin-like allosteric link between the binding pocket and the interdomain conformation can serve as the basis for the catch bond property of FimH and, possibly, other adhesive proteins.

Received for publication, September 18, 2007 , and in revised form, December 18, 2007.

^* This work was supported by grants from the National Institutes of Health, National Science Foundation, and ETH. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1.

¹ These authors contributed equally to this work.

² To whom correspondence may be addressed. Tel.: 206-616-3947; Fax: 206-685-4434; E-mail: wendyt{at}u.washington.edu.

³ To whom correspondence may be addressed. Tel.: 206-685-2162; Fax: 206-543-8297; E-mail: evs{at}u.washington.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. S. Ronald, O. Yakovenko, N. Yazvenko, S. Chattopadhyay, P. Aprikian, W. E. Thomas, and E. V. Sokurenko From the Cover: Adaptive mutations in the signal peptide of the type 1 fimbrial adhesin of uropathogenic Escherichia coli PNAS, August 5, 2008; 105(31): 10937 - 10942. [Abstract] [Full Text] [PDF]

				O. Yakovenko, S. Sharma, M. Forero, V. Tchesnokova, P. Aprikian, B. Kidd, A. Mach, V. Vogel, E. Sokurenko, and W. E. Thomas FimH Forms Catch Bonds That Are Enhanced by Mechanical Force Due to Allosteric Regulation J. Biol. Chem., April 25, 2008; 283(17): 11596 - 11605. [Abstract] [Full Text] [PDF]