Interaction between collagen and the α2 I-domain of integrin αβ1: Critical role of conserved residues in the metal ion-dependent adhesion site (MIDAS) region

Tetsuji Kamata, Robert C. Liddington, Yoshikazu Takada

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

A docking model of the α2 I-domain and collagen has been proposed based on their crystal structures (Emsley, J., King, S., Bergelson, J., and Liddington, R. C. (1997) J. Biol. Chem. 272, 28512-28517). In this model, several amino acid residues in the I-domain make direct contact with collagen (Asn-154, Asp-219, Leu-220, Glu256, His-258, Tyr-285, Asn-289, Leu-291, Asn- 295, and Lys-298), and the protruding C-helix of α2 (residues 284-288) determines ligand specificity. Because most of the proposed critical residues are not conserved, different I-domains are predicted to bind to collagen differently. We found that deleting the entire C-helix or mutating the predicted critical residues had no effect on collagen binding to whole α2β1, with the exception that mutating Asn-154, Asp-219, and His-258 had a moderate effect. We performed further studies and found that mutating the conserved surface-exposed residues in the metal ion-dependent adhesion site (MIDAS) (Tyr-157 and Gln-215) significantly blocks collagen binding. We have revised the docking model based on the mutagenesis data. In the revised model, conserved Tyr-157 makes contact with collagen in addition to the previously proposed Asn-154, Asp-219, His-258, and Tyr-285 residues. These results suggest that the collagen-binding I-domains (e.g. α1, α2, and α10) bind to collagen in a similar fashion.

Original languageEnglish
Pages (from-to)32108-32111
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number45
DOIs
Publication statusPublished - Nov 5 1999
Externally publishedYes

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Integrins
Metal ions
Collagen
Adhesion
Metals
Ions
Mutagenesis
Crystal structure
Ligands
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Interaction between collagen and the α2 I-domain of integrin αβ1 : Critical role of conserved residues in the metal ion-dependent adhesion site (MIDAS) region. / Kamata, Tetsuji; Liddington, Robert C.; Takada, Yoshikazu.

In: Journal of Biological Chemistry, Vol. 274, No. 45, 05.11.1999, p. 32108-32111.

Research output: Contribution to journalArticle

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