Untangling Desmosomal Knots With Electron Tomography

Science. 2003 Oct 3;302(5642):109-13. doi: 10.1126/science.1086957.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cadherins / chemistry*
  • Cadherins / ultrastructure*
  • Cell Adhesion
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / ultrastructure
  • Desmoplakins
  • Desmosomes / chemistry*
  • Desmosomes / ultrastructure*
  • Dimerization
  • Epidermis / chemistry
  • Epidermis / ultrastructure
  • Freeze Substitution
  • Hydrophobic and Hydrophilic Interactions
  • Image Processing, Computer-Assisted*
  • Mice
  • Microscopy, Electron / methods
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Tomography*
  • Tryptophan / chemistry
  • Xenopus Proteins

Substances

  • CDH3 protein, Xenopus
  • Cadherins
  • Cytoskeletal Proteins
  • Desmoplakins
  • Xenopus Proteins
  • Tryptophan

Associated data

  • PDB/1Q55
  • PDB/1Q5A
  • PDB/1Q5B
  • PDB/1Q5C