PDBsum entry 5j5j

Cell adhesion

PDB id: 5j5j

Contents

Protein chain

552 a.a.

Ligands

NAG-NAG-BMA-MAN-NAG-GAL-MAN-NAG

NAG-NAG-BMA-MAN-MAN-FUC

NAG-NAG

MAN ×3

NAG ×2

Metals

_CL ×2

_CA ×11

Waters ×9

PDB id:

5j5j

Name:

Cell adhesion

Title:

Crystal structure of a chimera of human desmocollin-2 ec1 and human desmoglein-2 ec2-ec5

Structure:

Desmocollin-2,desmoglein-2. Chain: a. Fragment: unp residues 136-235. Unp residues 152-601. Synonym: cadherin family member 2,desmocollin-3,desmosomal glycoprotein ii,desmosomal glycoprotein iii,cadherin family member 5, hdgc. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dsc2, cdhf2, dsc3, dsg2, cdhf5. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293

Resolution:

3.29Å R-factor: 0.249 R-free: 0.285

Authors:

J.Brasch,O.J.Harrison,L.Shapiro

Key ref:

O.J.Harrison et al. (2016). Structural basis of adhesive binding by desmocollins and desmogleins. Proc Natl Acad Sci U S A, 113, 7160-7165. PubMed id: 27298358 DOI: 10.1073/pnas.1606272113

Date:

02-Apr-16 Release date: 22-Jun-16

Protein chain

Q02487  (DSC2_HUMAN) -  Desmocollin-2 from Homo sapiens

Seq: 901 a.a.

Struc: 552 a.a.*

Protein chain

Q14126  (DSG2_HUMAN) -  Desmoglein-2 from Homo sapiens

Seq: 1118 a.a.

Struc: 552 a.a.*

* PDB and UniProt seqs differ at 386 residue positions (black crosses)

DOI no: 10.1073/pnas.1606272113

Proc Natl Acad Sci U S A 113:7160-7165 (2016)

PubMed id: 27298358

Structural basis of adhesive binding by desmocollins and desmogleins.

O.J.Harrison, J.Brasch, G.Lasso, P.S.Katsamba, G.Ahlsen, B.Honig, L.Shapiro.

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.