The molecular architecture of cadherins in native epidermal desmosomes

• Published in: Nature Vol. 450; no. 7171; pp. 832 - 837
• Main Authors: AL-AMOUDI, Ashraf, CASTANO DIEZ, Daniel, BETTS, Matthew J, FRANGAKIS, Achilleas S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 06.12.2007; Nature Publishing Group
• Subjects: Adhesion; Architecture; Arrays; Atomic structure; Biological and medical sciences; Biomedical research; Biopsy; Cadherins - chemistry; Cadherins - ultrastructure; Cell adhesion & migration; Cryoultramicrotomy; Crystallography, X-Ray; Density; Desmosomes - chemistry; Desmosomes - ultrastructure; Epidermis; Epidermis - chemistry; Epidermis - cytology; Epidermis - ultrastructure; Fundamental and applied biological sciences. Psychology; Humans; Male; Membranes; Microscopy, Electron; Models, Molecular; Molecular biophysics; Molecular structure; Organizations; Reconstruction; Skin; Structure in molecular biology; Supramolecular structure; Three dimensional; Tomography; Human; Epidermis; Desmosome; Cadherin; Molecular architecture; Cell adhesion
• ISSN: 0028-0836; 1476-4687; 1476-4679
• 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.