The role of α and β chains in ligand recognition by β7 integrins

J. M G Higgins, M. Cernadas, K. Tan, A. Irie, J. H. Wang, Yoshikazu Takada, M. B. Brenner

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Integrins α(E)β7 and α4β7 are involved in localization of leukocytes at mucosal sites. Although both α(E)β7 and α4β7 utilize the β7 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 α(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 I indicates that coordination of the α(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 α(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 β7 MIDAS motif (D140A) abolished α(E)β7 binding to E-cadherin and α4β7-mediated adhesion to MAdCAM-1, and α4 chain mutations that abrogated binding of α4β1 to vascular cell adhesion molecule-1 and fibronectin similarly reduced α4β7 interaction with MAdCAM-1. Thus, although specificity can be determined by the integrin α or β chain, common structural features of both subunits are required for recognition of dissimilar ligands.

Original languageEnglish (US)
Pages (from-to)25652-25664
Number of pages13
JournalJournal of Biological Chemistry
Volume275
Issue number33
DOIs
StatePublished - Aug 18 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Higgins, J. M. G., Cernadas, M., Tan, K., Irie, A., Wang, J. H., Takada, Y., & Brenner, M. B. (2000). The role of α and β chains in ligand recognition by β7 integrins. Journal of Biological Chemistry, 275(33), 25652-25664. https://doi.org/10.1074/jbc.M001228200