Untangling desmosomal knots with electron tomography.
Cell adhesion by adherens junctions and desmosomes relies on interactions between cadherin molecules. However, the molecular interfaces that define molecular specificity and that mediate adhesion remain controversial. We used electron tomography of plastic sections from neonatal mouse skin to visualize the organization of desmosomes in situ. The resulting three-dimensional maps reveal individual cadherin molecules forming discrete groups and interacting through their tips. Fitting of an x-ray crystal structure for C-cadherin to these maps is consistent with a flexible intermolecular interface mediated by an exchange of amino-terminal tryptophans. This flexibility suggests a novel mechanism for generating both cis and trans interactions and for propagating these adhesive interactions along the junction.
He
Wanzhong
W
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA..
Cowin
Pamela
P
Stokes
David L
DL
D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000737:chemistry* / Q000648:ultrastructure*; D002448:Cell Adhesion; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000648:ultrastructure; D051180:Desmoplakins; D003896:Desmosomes / Q000737:chemistry* / Q000648:ultrastructure*; D019281:Dimerization; D004817:Epidermis / Q000737:chemistry / Q000648:ultrastructure; D017110:Freeze Substitution; D057927:Hydrophobic and Hydrophilic Interactions; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008854:Microscopy, Electron / Q000379:methods; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014054:Tomography; D014364:Tryptophan / Q000737:chemistry; D029867:Xenopus Proteins
C074260:CDH3 protein, Xenopus; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D029867:Xenopus Proteins; D014364:Tryptophan