Structural basis of integrin-mediated signal transduction

Yoshikazu Takada, Tetsuji Kamata, Atsushi Irie, Wilma Puzon-McLaughlin, Xi Ping Zhang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Integrins are a family of α/β heterodimers of cell adhesion receptors that mediate cell-extracellular matrix and cell-cell interactions. Both α and β subunits have a large extracellular domain and a short cytoplasmic domain. The α subunit has seven sequence repeats of 60-70 residues in its N-terminal region. The β-propeller model, in which seven four-stranded β-sheets are arranged in a torus around a pseudosymmetry axis, has been proposed as a structural model of these seven repeats. Several predicted loops critical for ligand binding have been identified in the upper face of the proposed β-propeller model. Several α subunits (e.g., α2, αL and αM) have I-domains of about 200 residues inserted between their second and third repeats. These I-domains adopt a Rossman-fold structure and have major ligand and cation binding sites (the MIDAS site) on their surfaces. The β subunit has an I-domain-like structure in its N-terminal region. This structure includes multiple sequences/conserved oxygenated residues critical for ligand binding, and non-conserved residues critical for ligand specificities. Several 'activation-dependent' epitopes have been identified in the Cys-rich (stalk) region of β1. It has yet to be determined how these multiple ligand binding sites in the α and β subunits are involved in ligand binding, and how conformational changes on activation/ligand occupancy relate to signal transduction.

Original languageEnglish
Pages (from-to)143-151
Number of pages9
JournalMatrix Biology
Volume16
Issue number4
DOIs
Publication statusPublished - Oct 1997
Externally publishedYes

Keywords

  • Integrin
  • Ligand binding
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology

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    Takada, Y., Kamata, T., Irie, A., Puzon-McLaughlin, W., & Zhang, X. P. (1997). Structural basis of integrin-mediated signal transduction. Matrix Biology, 16(4), 143-151. https://doi.org/10.1016/S0945-053X(97)90002-0