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

J. Biol. Chem., Vol. 282, Issue 33, 23970-23980, August 17, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/33/23970    most recent M700921200v1 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 Li, Y.-F. Articles by Xia, D. Search for Related Content PubMed PubMed Citation Articles by Li, Y.-F. Articles by Xia, D. Social Bookmarking                      What's this?

A Receptor-binding Site as Revealed by the Crystal Structure of CfaE, the Colonization Factor Antigen I Fimbrial Adhesin of Enterotoxigenic Escherichia coli^*

Yong-Fu Li, Steven Poole, Fatima Rasulova, Annette L. McVeigh, Stephen J. Savarino^¶1, and Di Xia²

From the Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892-4256, the Enteric Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, Maryland 20910-7500, and the ^¶Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799

CfaE is the minor, tip-localized adhesive subunit of colonization factor antigen I fimbriae (CFA/I) of enterotoxigenic Escherichia coli and is thought to be essential for the attachment of enterotoxigenic E. coli to the human small intestine early in diarrhea pathogenesis. The crystal structure of an in cis donor strand complemented CfaE was determined, providing the first atomic view of a fimbrial subunit assembled by the alternate chaperone pathway. The in cis donor strand complemented variant of CfaE structure consists of an N-terminal adhesin domain and a C-terminal pilin domain of similar size, each featuring a variable immunoglobulin-like fold. Extensive interactions exist between the two domains and appear to rigidify the molecule. The upper surface of the adhesin domain distal to the pilin domain reveals a depression consisting of conserved residues including Arg¹⁸¹, previously shown to be necessary for erythrocyte adhesion. Mutational analysis revealed a cluster of conserved, positively charged residues that are required for CFA/I-mediated hemagglutination, implicating this as the receptor-binding pocket. Mutations in a few subclass-specific residues that surround the cluster displayed differential effects on the two red cell species used in hemagglutination, suggesting that these residues play a role in host or cell specificity. The C-terminal donor strand derived from the major subunit CfaB is folded as a -strand and fits into a hydrophobic groove in the pilin domain to complete the immunoglobulin fold. The location of this well ordered donor strand suggests the positioning and orientation of the subjacent major fimbrial subunit CfaB in the native assembly of CFA/I fimbriae.

Received for publication, January 31, 2007 , and in revised form, June 5, 2007.

^* This work was supported in part by the Intramural Research Program of the NCI, National Institutes of Health (NIH), Center for Cancer Research, by a research grant from NIAID (to D. X.), by the U.S. Army Military Infectious Diseases Research Program, Work Unit Number A0307 (to S. J. S.), and by the Henry M. Jackson Foundation for the Advancement of Military Medicine (to S. J. S.), which employs S. P., F. R., and A. L. M. 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 atomic coordinates and structure factors (code 2HB0) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

The on-line version of this article (available at http://www.jbc.org) contains supplemental text, Tables S1 and S2, Figs. S1–S3, and Refs. 1 and 2.

¹ To whom correspondence may be addressed: U.S. Naval Medical Research Center, 503 Robert Grant Ave., Silver Spring, MD 20910. Tel.: 301-319-7650; Fax: 301-319-7679; E-mail: savarinos{at}nmrc.navy.mil. ²To whom correspondence may be addressed: Laboratory of Cell Biology, NCI, NIH, 37 Convent Dr., Bldg. 37, Rm. 2122C, Bethesda, MD 20892. Tel.: 301-435-6315; Fax: 301-480-2315; E-mail: dixia{at}helix.nih.gov.

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

This article has been cited by other articles:

				Y.-F. Li, S. Poole, K. Nishio, K. Jang, F. Rasulova, A. McVeigh, S. J. Savarino, D. Xia, and E. Bullitt Structure of CFA/I fimbriae from enterotoxigenic Escherichia coli PNAS, June 30, 2009; 106(26): 10793 - 10798. [Abstract] [Full Text] [PDF]