The molecular architecture of cadherins in native epidermal desmosomes

Nature. 2007 Dec 6;450(7171):832-7. doi: 10.1038/nature05994.


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 approximately 70 A 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Cadherins / chemistry
  • Cadherins / ultrastructure*
  • Cryoultramicrotomy
  • Crystallography, X-Ray
  • Desmosomes / chemistry
  • Desmosomes / ultrastructure*
  • Epidermal Cells*
  • Epidermis / chemistry
  • Epidermis / ultrastructure*
  • Humans
  • Male
  • Microscopy, Electron
  • Models, Molecular
  • Tomography


  • Cadherins