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C-terminal opening mimics 'inside-out' activation of integrin alpha5beta1.

Publication ,  Journal Article
Takagi, J; Erickson, HP; Springer, TA
Published in: Nat Struct Biol
May 2001

Integrins are adhesion molecules that convey signals both to and from the cytoplasm across the plasma membrane. In resting cells, integrins in a low affinity state can be activated by 'inside-out signaling', in which signals affecting integrin heterodimer cytoplasmic domains cause a conformational change in the integrin ligand-binding headpiece connected to the membrane by two long, approximately 16 nm stalks. Here we demonstrate a mechanism for conveying a conformational change over the long distance from the plasma membrane to the headpiece. We prepared soluble, alpha5beta1 integrin heterodimer extracellular fragments in which interactions between alpha- and beta-subunit cytoplasmic domains were replaced with an artificial clasp. Release of this C-terminal clasp by specific protease cleavage resulted in an approximately 14 nm separation of the stalks coupled to increased binding to fibronectin. This activation did not require any associated molecules or clustering and was observed with physiological concentrations of divalent cations. These findings suggest that the overall mechanism for integrin inside-out activation involves the spatial separation of the cytoplasmic and/or transmembrane domains.

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Published In

Nat Struct Biol

DOI

ISSN

1072-8368

Publication Date

May 2001

Volume

8

Issue

5

Start / End Page

412 / 416

Location

United States

Related Subject Headings

  • Solubility
  • Signal Transduction
  • Receptors, Fibronectin
  • Protein Subunits
  • Protein Structure, Tertiary
  • Protein Engineering
  • Protein Binding
  • Peptide Fragments
  • Molecular Sequence Data
  • Models, Biological
 

Citation

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Takagi, J., Erickson, H. P., & Springer, T. A. (2001). C-terminal opening mimics 'inside-out' activation of integrin alpha5beta1. Nat Struct Biol, 8(5), 412–416. https://doi.org/10.1038/87569
Takagi, J., H. P. Erickson, and T. A. Springer. “C-terminal opening mimics 'inside-out' activation of integrin alpha5beta1.Nat Struct Biol 8, no. 5 (May 2001): 412–16. https://doi.org/10.1038/87569.
Takagi J, Erickson HP, Springer TA. C-terminal opening mimics 'inside-out' activation of integrin alpha5beta1. Nat Struct Biol. 2001 May;8(5):412–6.
Takagi, J., et al. “C-terminal opening mimics 'inside-out' activation of integrin alpha5beta1.Nat Struct Biol, vol. 8, no. 5, May 2001, pp. 412–16. Pubmed, doi:10.1038/87569.
Takagi J, Erickson HP, Springer TA. C-terminal opening mimics 'inside-out' activation of integrin alpha5beta1. Nat Struct Biol. 2001 May;8(5):412–416.

Published In

Nat Struct Biol

DOI

ISSN

1072-8368

Publication Date

May 2001

Volume

8

Issue

5

Start / End Page

412 / 416

Location

United States

Related Subject Headings

  • Solubility
  • Signal Transduction
  • Receptors, Fibronectin
  • Protein Subunits
  • Protein Structure, Tertiary
  • Protein Engineering
  • Protein Binding
  • Peptide Fragments
  • Molecular Sequence Data
  • Models, Biological