Year: 2016
Type: article
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.
Institutions: Howard Hughes Medical Institute, Columbia University
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Storage System for High Performance Computing, G2686365521, Molecular basis of Cadherin Mediated Cell Adhesion, High-performance compute cluster for biomedical computing, Computer Studies of Protein Structure and Function, Structure and Function of Desmosomal Cadherins, G8682720686, The Molecular Basis of Cadherin-Mediated Cell Adhesion, NE-CAT Center for Advanced Macromolecular Crystallography, G9000119994, G9000281410
OpenAlex ID: W2432757814