The molecular architecture of cadherins in native epidermal desmosomes

Ashraf Al-Amoudi, Daniel Castaño Díez, Matthew J. Betts and Achilleas S. Frangakis ()
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Ashraf Al-Amoudi: European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany
Daniel Castaño Díez: European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany
Matthew J. Betts: European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany
Achilleas S. Frangakis: European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany

Nature, 2007, vol. 450, issue 7171, 832-837

Abstract: Abstract Desmosomes are cadherin-based adhesive intercellular junctions, which are present in tissues such as heart and skin. Despite considerable efforts, the molecular interfaces that mediate adhesion remain obscure. Here we apply cryo-electron tomography of vitreous sections from human epidermis to visualize the three-dimensional molecular architecture of desmosomal cadherins at close-to-native conditions. The three-dimensional reconstructions show a regular array of densities at ∼70 Å intervals along the midline, with a curved shape resembling the X-ray structure of C-cadherin, a representative ‘classical’ cadherin. Model-independent three-dimensional image processing of extracted sub-tomograms reveals the cadherin organization. After fitting the C-cadherin atomic structure into the averaged sub-tomograms, we see a periodic arrangement of a trans W-like and a cis V-like interaction corresponding to molecules from opposing membranes and the same cell membrane, respectively. The resulting model of cadherin organization explains existing two-dimensional data and yields insights into a possible mechanism of cadherin-based cell adhesion.

Date: 2007
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DOI: 10.1038/nature05994

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