The molecular architecture of cadherins in native epidermal desmosomes.
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.
European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany.
Ashraf
A
Al-Amoudi
Daniel Castaño
DC
Díez
Matthew J
MJ
Betts
Achilleas S
AS
Frangakis
D001706:Biopsy; D015820:Cadherins / Q000737:chemistry / Q000648:ultrastructure*; D016616:Cryoultramicrotomy; D018360:Crystallography, X-Ray; D003896:Desmosomes / Q000737:chemistry / Q000648:ultrastructure*; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry / Q000648:ultrastructure*; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008958:Models, Molecular; D014054:Tomography
D015820:Cadherins