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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 beta integrin subunit. Here, we report the first structure of talin bound to an authentic full-length beta 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 beta tail disrupts an integrin alpha/beta 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 publication

DOI

10.1038/emboj.2009.287

Type

Journal article

Journal

EMBO J

Publication Date

18/11/2009

Volume

28

Pages

3623 - 3632

Keywords

Amino Acid Sequence, Animals, CHO Cells, Cell Membrane, Cell Polarity, Cricetinae, Cricetulus, Integrins, Macromolecular Substances, Models, Biological, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Signal Transduction, Talin