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Structure of a double ubiquitin‐like domain in the talin head: a role in integrin activation

Benjamin T Goult, Mohamed Bouaouina, Paul R Elliott, Neil Bate, Bipin Patel, Alexandre R Gingras, J Günter Grossmann, Gordon C K Roberts, David A Calderwood, David R Critchley, Igor L Barsukov

Author Affiliations

  1. Benjamin T Goult1,
  2. Mohamed Bouaouina2,
  3. Paul R Elliott3,
  4. Neil Bate1,
  5. Bipin Patel1,
  6. Alexandre R Gingras1,
  7. J Günter Grossmann3,
  8. Gordon C K Roberts1,
  9. David A Calderwood2,
  10. David R Critchley*,1 and
  11. Igor L Barsukov*,3
  1. 1 Department of Biochemistry, University of Leicester, Leicester, UK
  2. 2 Department of Pharmacology and Interdepartmental Program in Vascular Biology and Transplantation, Yale University School of Medicine, New Haven, CT, USA
  3. 3 School of Biological Sciences, University of Liverpool, Liverpool, UK
  1. *Corresponding authors: School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, UK. Tel.: +44 151 795 4307; Fax: +44 151 795 4414; E-mail: igb2{at} of Biochemistry, University of Leicester, Leicester L69 7ZB, UK. Tel.: +44 116 229 7099; Fax: +44 116 229 7099; E-mail: drc{at}
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Talin is a 270‐kDa protein that activates integrins and couples them to cytoskeletal actin. Talin contains an N‐terminal FERM domain comprised of F1, F2 and F3 domains, but it is atypical in that F1 contains a large insert and is preceded by an extra domain F0. Although F3 contains the binding site for β‐integrin tails, F0 and F1 are also required for activation of β1‐integrins. Here, we report the solution structures of F0, F1 and of the F0F1 double domain. Both F0 and F1 have ubiquitin‐like folds joined in a novel fixed orientation by an extensive charged interface. The F1 insert forms a loop with helical propensity, and basic residues predicted to reside on one surface of the helix are required for binding to acidic phospholipids and for talin‐mediated activation of β1‐integrins. This and the fact that basic residues on F2 and F3 are also essential for integrin activation suggest that extensive interactions between the talin FERM domain and acidic membrane phospholipids are required to orientate the FERM domain such that it can activate integrins.

  • Received September 22, 2009.
  • Accepted January 11, 2010.
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This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.

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