Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M001228200 on June 2, 2000

J. Biol. Chem., Vol. 275, Issue 33, 25652-25664, August 18, 2000
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
275/33/25652    most recent
M001228200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Higgins, J. M. G.
Right arrow Articles by Brenner, M. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Higgins, J. M. G.
Right arrow Articles by Brenner, M. B.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

The Role of alpha  and beta  Chains in Ligand Recognition by beta 7 Integrins*

Jonathan M. G. HigginsDagger §, Manuela CernadasDagger , Kemin Tan||, Atsushi Irie**, Jia-huai Wang||, Yoshikazu Takada**, and Michael B. BrennerDagger

From the Dagger  Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, and the  Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School and the || Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115 and the ** Department of Vascular Biology, Scripps Research Institute, La Jolla, California 92037

Integrins alpha Ebeta 7 and alpha 4beta 7 are involved in localization of leukocytes at mucosal sites. Although both alpha Ebeta 7 and alpha 4beta 7 utilize the beta 7 chain, they have distinct binding specificities for E-cadherin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1), respectively. We found that mutation of the metal ion-dependent adhesion site (MIDAS) in the alpha E A-domain (D190A) abolished E-cadherin binding, as did mutation F298A on the A-domain surface near the MIDAS cleft. A docking model of the A-domain with E-cadherin domain 1 indicates that coordination of the alpha E MIDAS metal ion by E-cadherin Glu31 and a novel projection of Phe298 into a hydrophobic pocket on E-cadherin provide the basis for the interaction. The location of the binding site on the alpha E A-domain resembles that on other integrins, but its structure appears distinctive and particularly adapted to recognize the tip of E-cadherin, a unique integrin ligand. Additionally, mutation of the beta 7 MIDAS motif (D140A) abolished alpha Ebeta 7 binding to E-cadherin and alpha 4beta 7-mediated adhesion to MAdCAM-1, and alpha 4 chain mutations that abrogated binding of alpha 4beta 1 to vascular cell adhesion molecule-1 and fibronectin similarly reduced alpha 4beta 7 interaction with MAdCAM-1. Thus, although specificity can be determined by the integrin alpha  or beta  chain, common structural features of both subunits are required for recognition of dissimilar ligands.

* This work was supported by grants from the Crohn's and Colitis Foundation of America (to J. M. G. H.) and the National Institutes of Health (to M. B. B., Y. T., and J.-h. W.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed: Brigham and Women's Hospital, Smith Bldg., Rm. 538D, One Jimmy Fund Way, Boston, MA 02115. Tel.: 617-525-1105; Fax: 617-525-1010; E-mail: jhiggins@rics.bwh.harvard.edu. The atomic coordinates of the human E-cadherin domain 1 and alpha E A-domain models are available upon request.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
L. Charrier, Y. Yan, H. T. T. Nguyen, G. Dalmasso, C. L. Laboisse, A. T. Gewirtz, S. V. Sitaraman, and D. Merlin
ADAM-15/Metargidin Mediates Homotypic Aggregation of Human T Lymphocytes and Heterotypic Interactions of T Lymphocytes with Intestinal Epithelial Cells
J. Biol. Chem., June 8, 2007; 282(23): 16948 - 16958.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
H. P. Kiener, D. M. Lee, S. K. Agarwal, and M. B. Brenner
Cadherin-11 Induces Rheumatoid Arthritis Fibroblast-Like Synoviocytes to Form Lining Layers in Vitro
Am. J. Pathol., May 1, 2006; 168(5): 1486 - 1499.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
K. L. Graham, F. E. Fleming, P. Halasz, M. J. Hewish, H. S. Nagesha, I. H. Holmes, Y. Takada, and B. S. Coulson
Rotaviruses interact with {alpha}4{beta}7 and {alpha}4{beta}1 integrins by binding the same integrin domains as natural ligands
J. Gen. Virol., December 1, 2005; 86(12): 3397 - 3408.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Shiraishi, K. Tsuzaka, K. Yoshimoto, C. Kumazawa, K. Nozaki, T. Abe, K. Tsubota, and T. Takeuchi
Critical Role of the Fifth Domain of E-Cadherin for Heterophilic Adhesion with {alpha}E{beta}7, But Not for Homophilic Adhesion
J. Immunol., July 15, 2005; 175(2): 1014 - 1021.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
C. A. Whittaker and R. O. Hynes
Distribution and Evolution of von Willebrand/Integrin A Domains: Widely Dispersed Domains with Roles in Cell Adhesion and Elsewhere
Mol. Biol. Cell, October 1, 2002; 13(10): 3369 - 3387.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Wright, A. Hidalgo, J. M. Rodriguez-Frade, S. F. Soriano, M. Mellado, M. Parmo-Cabanas, M. J. Briskin, and J. Teixido
The Chemokine Stromal Cell-Derived Factor-1{alpha} Modulates {alpha}4{beta}7 Integrin-Mediated Lymphocyte Adhesion to Mucosal Addressin Cell Adhesion Molecule-1 and Fibronectin
J. Immunol., May 15, 2002; 168(10): 5268 - 5277.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
U. G. Strauch, R. C. Mueller, X. Y. Li, M. Cernadas, J. M. G. Higgins, D. G. Binion, and C. M. Parker
Integrin {{alpha}}E(CD103){{beta}}7 Mediates Adhesion to Intestinal Microvascular Endothelial Cell Lines Via an E-Cadherin-Independent Interaction
J. Immunol., March 1, 2001; 166(5): 3506 - 3514.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Corps, C. Carter, P. Karecla, T. Ahrens, P. Evans, and P. Kilshaw
Recognition of E-cadherin by Integrin alpha Ebeta 7. REQUIREMENT FOR CADHERIN DIMERIZATION AND IMPLICATIONS FOR CADHERIN AND INTEGRIN FUNCTION
J. Biol. Chem., August 10, 2001; 276(33): 30862 - 30870.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement