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Updated: Mar 19, 2026

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
Published on: October 17, 2014
Structural basis of adhesive binding by desmocollins and desmogleins
Oliver J Harrison1, Julia Brasch2, Gorka Lasso3
1Department of Systems Biology, Columbia University, New York, NY 10032; Howard Hughes Medical Institute, Columbia University, New York, NY 10032;
Abstract:
Desmosomes are intercellular adhesive junctions that impart strength to vertebrate tissues. Their dense, ordered intercellular attachments are formed by desmogleins (Dsgs) and desmocollins (Dscs), but the nature of trans-cellular interactions between these specialized cadherins is unclear. Here, using solution biophysics and coated-bead aggregation experiments, we demonstrate family-wise heterophilic specificity: All Dsgs form adhesive dimers with all Dscs, with affinities characteristic of each Dsg:Dsc pair. Crystal structures of ectodomains from Dsg2 and Dsg3 and from Dsc1 and Dsc2 show binding through a strand-swap mechanism similar to that of homophilic classical cadherins. However, conserved charged amino acids inhibit Dsg:Dsg and Dsc:Dsc interactions by same-charge repulsion and promote heterophilic Dsg:Dsc interactions through opposite-charge attraction. These findings show that Dsg:Dsc heterodimers represent the fundamental adhesive unit of desmosomes and provide a structural framework for understanding desmosome assembly.
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