5EQX

Crystal structure of human Desmoglein-3 ectodomain

Summary for 5EQX

• Entry DOI: 10.2210/pdb5eqx/pdb
• Related: 5ERD 5ERP
• Descriptor: Desmoglein-3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: extracellular cadherin domain, cell adhesion, cell surface, desmosome
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 63474.22

Authors

Harrison, O.J.,Brasch, J.,Shapiro, L. (deposition date: 2015-11-13, release date: 2016-06-15, Last modification date: 2020-07-29)

Primary citation

Harrison, O.J.,Brasch, J.,Lasso, G.,Katsamba, P.S.,Ahlsen, G.,Honig, B.,Shapiro, L.
Structural basis of adhesive binding by desmocollins and desmogleins.
Proc.Natl.Acad.Sci.USA, 113:7160-7165, 2016

PubMed 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.

PubMed: 27298358
DOI: 10.1073/pnas.1606272113

Experimental method

X-RAY DIFFRACTION (3.05 Å)