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

J. Biol. Chem., Vol. 282, Issue 32, 23437-23446, August 10, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/32/23437    most recent M702037200v1 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 Aprikian, P. Articles by Sokurenko, E. Search for Related Content PubMed PubMed Citation Articles by Aprikian, P. Articles by Sokurenko, E. Social Bookmarking                      What's this?

Interdomain Interaction in the FimH Adhesin of Escherichia coli Regulates the Affinity to Mannose^*

Pavel Aprikian¹, Veronika Tchesnokova¹, Brian Kidd, Olga Yakovenko, Vladimir Yarov-Yarovoy^¶, Elena Trinchina, Viola Vogel^||, Wendy Thomas^**2, and Evgeni Sokurenko^**3

From the Departments of Microbiology, Bioengineering, ^¶Pharmacology, and ^**Nanotechnology Center, University of Washington, Seattle, Washington 98105 and the ^||Department of Materials, Laboratory of Biologically Oriented Materials, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland

FimH is a mannose-specific adhesin located on the tip of type 1 fimbriae of Escherichia coli that is capable of mediating shear-enhanced bacterial adhesion. FimH consists of a fimbria-associated pilin domain and a mannose-binding lectin domain, with the binding pocket positioned opposite the interdomain interface. By using the yeast two-hybrid system, purified lectin and pilin domains, and docking simulations, we show here that the FimH domains interact with one another. The affinity for mannose is greatly enhanced (up to 300-fold) in FimH variants in which the interdomain interaction is disrupted by structural mutations in either the pilin or lectin domains. Also, affinity to mannose is dramatically enhanced in isolated lectin domains or in FimH complexed with the chaperone molecule that is wedged between the domains. Furthermore, FimH with native structure mediates weak binding at low shear stress but shifts to strong binding at high shear, whereas FimH with disrupted interdomain contacts (or the isolated lectin domain) mediates strong binding to mannose-coated surfaces even under low shear. We propose that interactions between lectin and pilin domains decrease the affinity of the mannose-binding pocket via an allosteric mechanism. We further suggest that mechanical force at high shear stress separates the two domains, allowing the lectin domain to switch from a low affinity to a high affinity state. This shift provides a mechanism for FimH-mediated shear-enhanced adhesion by enabling the adhesin to form catch bond-like interactions that are longer lived at high tensile force.

Received for publication, March 8, 2007 , and in revised form, June 13, 2007.

^* This work was supported by grants from the National Institutes of Health, National Science Foundation, and ETH (Swiss Federal Institute of Technology). 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 Figs. S1–S2, Table S1, and Movies 1–3.

¹ Both authors contributed equally to the study.

² To whom correspondence may be addressed: Dept. of Bioengineering, University of Washington, Seattle, WA, 98195. Tel.: 206-616-3947; E-mail: wendyt{at}u.washington.edu. ³ To whom correspondence may be addressed: Dept. of Microbiology, University of Washington, Seattle, WA 98195. 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]

				V. Tchesnokova, P. Aprikian, O. Yakovenko, C. LaRock, B. Kidd, V. Vogel, W. Thomas, and E. Sokurenko Integrin-like Allosteric Properties of the Catch Bond-forming FimH Adhesin of Escherichia coli J. Biol. Chem., March 21, 2008; 283(12): 7823 - 7833. [Abstract] [Full Text] [PDF]