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Research Themes Cancer

Cell Adhesion and Metastasis: Unraveling Talin

SBKB [doi:10.1038/sbkb.2014.209]
Featured Article - July 2014
Short description: In the absence of a 3D crystal structure of talin, a structural model based on EM reconstruction and known structures of individual domains provides insight into its mechanism of action.

EM reconstruction of full-length talin (left) and 3D model showing the flexible rods of two talin monomers in pink and white compacted in a donut shape, with respective N-terminal head domains in red and blue, occupying the center (right). Reprinted with permission from Elsevier 1 .

Talin is one of several proteins that activate integrins—transmembrane proteins involved in cell adhesion—and link them to the actin cytoskeleton. This adaptor protein comprises an N-terminal head domain, followed by a flexible rod made up of 62 α-helices organized into 13 domains, and a C-terminal dimerization helix.

Critchley, Volkmann, Hanein and colleagues (PSI CELLMAT) have solved structures of individual and combinations of talin domains by NMR spectroscopy or X-ray crystallography. By adding small-angle X-ray scattering data, they determined relative orientations of all domains within the full protein. This analysis revealed that the domains are connected by hinge-like linkers, which enable talin to flexibly connect to actin at various distances.

Purified full-size talin, however, exists as a compact, globular homodimer. Electron microscopy (EM) followed by single-particle reconstruction resulted in a three-dimensional (3D) reconstruction with ∼2.5-nm resolution after optimization. The rods were arranged in a donut shape, with the head domains occupying the center and thus burying the protein's integrin-binding site, rendering it inactive. NMR-based fragment-competition analysis confirmed known interactions and revealed new weak interactions in the auto-inhibited state of talin that were consistent with the EM model.

This modeling, combined with information from prior work, provides clues about how talin functions: the authors conclude that auto-inhibited talin must unravel in order to expose integrin-binding sites and connect with actin.

Irene Kaganman


  1. B.T. Goult et al. Structural studies on full-length talin1 reveal a compact auto-inhibited dimer: implications for talin activation.
    J. Struct. Biol. 184, 21-32 (2013). doi:10.1016/j.jsb.2013.05.014

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