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Two functional active conformations of the integrin α2β1, depending on activation condition and cell type

(2005) JOURNAL OF BIOLOGICAL CHEMISTRY. 280(44). p.36873-36882
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Organization
Abstract
For several integrins, the existence of multiple conformational states has been studied intensively. For the integrin alpha 2 beta 1, a major collagen receptor on platelets and other cell types, however, no such experimental data were available thus far. Recently, our group has developed a monoclonal antibody IAC-1 sensitive to the molecular conformation of alpha 2 beta 1 because it only binds to the activated state of alpha 2 beta 1 on platelets, induced upon inside-out signaling. By investigating IAC-1 binding in combination with collagen binding after inside-out stimulation and outside manipulation, we demonstrated the existence of three different conformations of alpha 2 beta 1 on platelets and Chinese hamster ovary cells as follows: (i) a nonactivated, resting state with no collagen nor IAC-1 binding; (ii) an intermediate state, induced by outside manipulation, with collagen but no IAC-1 binding; and (iii) a fully activated state, induced after inside-out stimulation, with both collagen and IAC-1 binding. Moreover, these different conformational states of alpha 2 beta 1 are dependent on the cell type where alpha 2 beta 1 is expressed, as IAC-1 binding to peripheral blood mononuclear cells and Jurkat cells could also be induced by outside manipulation, in contrast to platelets and alpha 2 beta 1-expressing Chinese hamster ovary cells. Finally, we revealed a functional relevance for these different conformational states because the conformation of alpha 2 beta 1, induced after outside manipulation, resulted in significantly more cell spreading on coated collagen compared with nonactivated or inside-out stimulated cells.
Keywords
HAMSTER OVARY CELLS, LIGAND-BINDING SITES, I-LIKE DOMAIN, MONOCLONAL-ANTIBODY, COLLAGEN RECEPTOR, CYTOPLASMIC DOMAINS, STRUCTURAL BASIS, GLYCOPROTEIN-VI, ALPHA(L)BETA(2) HYBRID DOMAIN, VON-WILLEBRAND-FACTOR

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MLA
Van de Walle, Gerlinde et al. “Two Functional Active Conformations of the Integrin Α2β1, Depending on Activation Condition and Cell Type.” JOURNAL OF BIOLOGICAL CHEMISTRY 280.44 (2005): 36873–36882. Print.
APA
Van de Walle, G., Vanhoorelbeke, K., Majer, Z., Illyés, E., Baert, J., Pareyn, I., & Deckmyn, H. (2005). Two functional active conformations of the integrin α2β1, depending on activation condition and cell type. JOURNAL OF BIOLOGICAL CHEMISTRY, 280(44), 36873–36882.
Chicago author-date
Van de Walle, Gerlinde, Karen Vanhoorelbeke, Zsuzsa Majer, Eszter Illyés, Johan Baert, Inge Pareyn, and Hans Deckmyn. 2005. “Two Functional Active Conformations of the Integrin Α2β1, Depending on Activation Condition and Cell Type.” Journal of Biological Chemistry 280 (44): 36873–36882.
Chicago author-date (all authors)
Van de Walle, Gerlinde, Karen Vanhoorelbeke, Zsuzsa Majer, Eszter Illyés, Johan Baert, Inge Pareyn, and Hans Deckmyn. 2005. “Two Functional Active Conformations of the Integrin Α2β1, Depending on Activation Condition and Cell Type.” Journal of Biological Chemistry 280 (44): 36873–36882.
Vancouver
1.
Van de Walle G, Vanhoorelbeke K, Majer Z, Illyés E, Baert J, Pareyn I, et al. Two functional active conformations of the integrin α2β1, depending on activation condition and cell type. JOURNAL OF BIOLOGICAL CHEMISTRY. 2005;280(44):36873–82.
IEEE
[1]
G. Van de Walle et al., “Two functional active conformations of the integrin α2β1, depending on activation condition and cell type,” JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 280, no. 44, pp. 36873–36882, 2005.
@article{934045,
  abstract     = {{For several integrins, the existence of multiple conformational states has been studied intensively. For the integrin alpha 2 beta 1, a major collagen receptor on platelets and other cell types, however, no such experimental data were available thus far. Recently, our group has developed a monoclonal antibody IAC-1 sensitive to the molecular conformation of alpha 2 beta 1 because it only binds to the activated state of alpha 2 beta 1 on platelets, induced upon inside-out signaling. By investigating IAC-1 binding in combination with collagen binding after inside-out stimulation and outside manipulation, we demonstrated the existence of three different conformations of alpha 2 beta 1 on platelets and Chinese hamster ovary cells as follows: (i) a nonactivated, resting state with no collagen nor IAC-1 binding; (ii) an intermediate state, induced by outside manipulation, with collagen but no IAC-1 binding; and (iii) a fully activated state, induced after inside-out stimulation, with both collagen and IAC-1 binding. Moreover, these different conformational states of alpha 2 beta 1 are dependent on the cell type where alpha 2 beta 1 is expressed, as IAC-1 binding to peripheral blood mononuclear cells and Jurkat cells could also be induced by outside manipulation, in contrast to platelets and alpha 2 beta 1-expressing Chinese hamster ovary cells. Finally, we revealed a functional relevance for these different conformational states because the conformation of alpha 2 beta 1, induced after outside manipulation, resulted in significantly more cell spreading on coated collagen compared with nonactivated or inside-out stimulated cells.}},
  author       = {{Van de Walle, Gerlinde and Vanhoorelbeke, Karen and Majer, Zsuzsa and Illyés, Eszter and Baert, Johan and Pareyn, Inge and Deckmyn, Hans}},
  issn         = {{0021-9258}},
  journal      = {{JOURNAL OF BIOLOGICAL CHEMISTRY}},
  keywords     = {{HAMSTER OVARY CELLS,LIGAND-BINDING SITES,I-LIKE DOMAIN,MONOCLONAL-ANTIBODY,COLLAGEN RECEPTOR,CYTOPLASMIC DOMAINS,STRUCTURAL BASIS,GLYCOPROTEIN-VI,ALPHA(L)BETA(2) HYBRID DOMAIN,VON-WILLEBRAND-FACTOR}},
  language     = {{eng}},
  number       = {{44}},
  pages        = {{36873--36882}},
  title        = {{Two functional active conformations of the integrin α2β1, depending on activation condition and cell type}},
  url          = {{http://dx.doi.org/10.1074/jbc.M508148200}},
  volume       = {{280}},
  year         = {{2005}},
}

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