The structure of an integrin/talin complex reveals the basis of inside-out signal transduction

Nicholas J. Anthis, Kate L. Wegener, Feng Ye, Chungho Kim, Benjamin T. Goult, Edward D. Lowe, Ioannis Vakonakis, Neil Bate, David R. Critchley, Mark H. Ginsberg, Iain D. Campbell

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209 Citations (Scopus)

Abstract

Fundamental to cell adhesion and migration, integrins are large heterodimeric membrane proteins that uniquely mediate inside-out signal transduction, whereby adhesion to the extracellular matrix is activated from within the cell by direct binding of talin to the cytoplasmic tail of the Β integrin subunit. Here, we report the first structure of talin bound to an authentic full-length Β integrin tail. Using biophysical and whole cell measurements, we show that a specific ionic interaction between the talin F3 domain and the membrane-proximal helix of the Β tail disrupts an integrin α/Β salt bridge that helps maintain the integrin inactive state. Second, we identify a positively charged surface on the talin F2 domain that precisely orients talin to disrupt the heterodimeric integrin transmembrane (TM) complex. These results show key structural features that explain the ability of talin to mediate inside-out TM signalling.

Original languageEnglish
Pages (from-to)3623-3632
Number of pages10
JournalEMBO Journal
Volume28
Issue number22
DOIs
Publication statusPublished - 2009 Nov

Keywords

  • Cell adhesion
  • Crystallography
  • Integrin activation
  • NMR
  • Talin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Anthis, N. J., Wegener, K. L., Ye, F., Kim, C., Goult, B. T., Lowe, E. D., Vakonakis, I., Bate, N., Critchley, D. R., Ginsberg, M. H., & Campbell, I. D. (2009). The structure of an integrin/talin complex reveals the basis of inside-out signal transduction. EMBO Journal, 28(22), 3623-3632. https://doi.org/10.1038/emboj.2009.287