The role of alpha and beta chains in ligand recognition by beta 7 integrins
| Autor: | J M, Higgins, M, Cernadas, K, Tan, A, Irie, J, Wang, Y, Takada, M B, Brenner |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Integrins Integrin beta Chains Phenylalanine Molecular Sequence Data Glutamic Acid Immunoglobulins Vascular Cell Adhesion Molecule-1 CHO Cells Ligands Transfection Protein Structure Secondary Mucoproteins Cricetinae Cell Adhesion Animals Humans Amino Acid Sequence Sequence Homology Amino Acid Antibodies Monoclonal Cadherins Flow Cytometry Precipitin Tests Fibronectins Protein Structure Tertiary Mutation Electrophoresis Polyacrylamide Gel K562 Cells Cell Adhesion Molecules Epitope Mapping Protein Binding |
| Zdroj: | The Journal of biological chemistry. 275(33) |
| ISSN: | 0021-9258 |
| Popis: | Integrins alpha(E)beta(7) and alpha(4)beta(7) are involved in localization of leukocytes at mucosal sites. Although both alpha(E)beta(7) and alpha(4)beta(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 Glu(31) and a novel projection of Phe(298) 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(E)beta(7) binding to E-cadherin and alpha(4)beta(7)-mediated adhesion to MAdCAM-1, and alpha(4) chain mutations that abrogated binding of alpha(4)beta(1) to vascular cell adhesion molecule-1 and fibronectin similarly reduced alpha(4)beta(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. |
| Databáze: | OpenAIRE |
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