The 'ligand-induced conformational change' of α5β1 integrin. Relocation of α5 subunit to uncover the β1 stalk region

Jun Tsuchida, Shoko Ueki, Yoshikazu Takada, Yuji Saito, Junichi Takagi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Integrin heterodimers undergo a conformational change upon the binding of ligand to their extracellular domains. An anti-β1 integrin monoclonal antibody AG89 can detect such a conformational change since it recognizes a ligand-inducible epitope in the stalk-like region of β1 subunits. The binding of a 125I-labeled AG89 Fab fragment to α5β1 integrins on K562 cells was assessed and analyzed by the Scatchard method. High affinity binding sites for AG89 are present on cells treated with ligand peptide. In addition, results revealed that cells treated with EDTA also express AG89 binding sites with the same affinity although the number of binding sites is 4-fold lower. AG89 immunoprecipitated α5β1 complexes from surface-labeled K562 cells treated with ligand peptide. By contrast, it immunoprecipitated only β1 chains when the ligand peptide was absent, suggesting that high affinity binding sites on EDTA-treated cells are associated with non-functional β1 monomer. Additional studies show that the epitope for AG89 is constitutively exposed on mutant β1 that cannot complex with α5. These data suggest that the AG89 epitope is masked by the α5 subunit. Ligand binding and integrin activation may uncover the β1 stalk region by triggering a conformational shift of α5 relative to β1.

Original languageEnglish
Pages (from-to)1759-1766
Number of pages8
JournalJournal of Cell Science
Volume111
Issue number12
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

Integrins
Ligands
Binding Sites
Epitopes
K562 Cells
Edetic Acid
Peptides
Immunoglobulin Fab Fragments
Monoclonal Antibodies

Keywords

  • Cell adhesion
  • Conformational change
  • Integrin
  • Ligand binding

ASJC Scopus subject areas

  • Cell Biology

Cite this

The 'ligand-induced conformational change' of α5β1 integrin. Relocation of α5 subunit to uncover the β1 stalk region. / Tsuchida, Jun; Ueki, Shoko; Takada, Yoshikazu; Saito, Yuji; Takagi, Junichi.

In: Journal of Cell Science, Vol. 111, No. 12, 1998, p. 1759-1766.

Research output: Contribution to journalArticle

Tsuchida, J, Ueki, S, Takada, Y, Saito, Y & Takagi, J 1998, 'The 'ligand-induced conformational change' of α5β1 integrin. Relocation of α5 subunit to uncover the β1 stalk region', Journal of Cell Science, vol. 111, no. 12, pp. 1759-1766.
Tsuchida, Jun ; Ueki, Shoko ; Takada, Yoshikazu ; Saito, Yuji ; Takagi, Junichi. / The 'ligand-induced conformational change' of α5β1 integrin. Relocation of α5 subunit to uncover the β1 stalk region. In: Journal of Cell Science. 1998 ; Vol. 111, No. 12. pp. 1759-1766.
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