Structural basis of adhesive binding by desmocollins and desmogleins

Oliver J. Harrison, Julia Brasch, Gorka Lasso, Phinikoula S. Katsamba, Goran Ahlsen, Barry Honig, Lawrence Shapiro

Research output: Contribution to journalArticle

48 Citations (Scopus)

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 oppositecharge attraction. These findings show that Dsg:Dsc heterodimers represent the fundamental adhesive unit of desmosomes and provide a structural framework for understanding desmosome assembly.

Original languageEnglish (US)
Pages (from-to)7160-7165
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number26
DOIs
StatePublished - Jun 28 2016
Externally publishedYes

Fingerprint

Desmocollins
Desmogleins
Desmosomes
Adhesives
Cadherins
Biophysics
Intercellular Junctions
Vertebrates
Amino Acids

Keywords

  • Cadherin
  • Cell adhesion
  • Desmosome
  • Heterophilic binding

ASJC Scopus subject areas

  • General

Cite this

Structural basis of adhesive binding by desmocollins and desmogleins. / Harrison, Oliver J.; Brasch, Julia; Lasso, Gorka; Katsamba, Phinikoula S.; Ahlsen, Goran; Honig, Barry; Shapiro, Lawrence.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 26, 28.06.2016, p. 7160-7165.

Research output: Contribution to journalArticle

Harrison, Oliver J. ; Brasch, Julia ; Lasso, Gorka ; Katsamba, Phinikoula S. ; Ahlsen, Goran ; Honig, Barry ; Shapiro, Lawrence. / Structural basis of adhesive binding by desmocollins and desmogleins. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 26. pp. 7160-7165.
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