Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique repeat motif structure

  title={Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique repeat motif structure},
  author={Hee-Jung Choi and Shaun Park-Snyder and Lauren T. Pascoe and Kathleen Janee Green and William I. Weis},
  journal={Nature Structural Biology},
Desmosomes are intercellular junctions in which cadherin cell adhesion molecules are linked to the intermediate filament (IF) system. Desmoplakin is a member of the plakin family of IF-binding proteins. The C-terminal domain of desmoplakin (DPCT) mediates binding to IFs in desmosomes. The DPCT sequence contains three regions, termed A, B and C, consisting of 4.5 copies of a 38-amino acid repeat motif. We demonstrate that these regions form discrete subdomains that bind to IFs and report the… 

Structure of the Intermediate Filament-Binding Region of Desmoplakin

The crystal structure of a DPCT fragment spanning PRDs A and B is presented, and the overall architecture of DPCT is elucidated by small angle X-ray scattering (SAXS) analysis, providing the first structural insights into an IF binding protein containing multiple PRDs.

Desmoplakin interacts with the coil 1 of different types of intermediate filament proteins and displays high affinity for assembled intermediate filaments

The data suggest that desmoplakin high-affinity binding to diverse IF proteins ensures robust linkages of IF cytoskeleton and desmosomes that maintain the structural integrity of cellular adhesion complexes.

Purification and Structural Analysis of Desmoplakin.

Claws, Disorder, and Conformational Dynamics of the C-Terminal Region of Human Desmoplakin.

It is suggested that DPCTT is a molecular switch that modulates, via its conformational dynamics, DP's overall efficacy as a substrate for GSK3, suggesting a competitive binding mechanism for the modulation of DP···IF interactions.

The desmosome.

The structure and function of the major desmosomal proteins are outlined, and the contributions of this protein complex to tissue architecture and morphogenesis are explored.

Structure, function, and regulation of desmosomes.

Mechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin

The crystal structure of envoplakin's complete PRD fold is reported, revealing binding determinants within its electropositive binding groove that reveal how plakin family members form dynamic linkages with cytoskeletal frameworks.

Molecular mechanism of intermediate filament recognition by plakin proteins.

Advances and perspectives of the architecture of hemidesmosomes: Lessons from structural biology

The formation of the β4-plectin complex induces conformational changes in β4 and plectin, suggesting that their interaction may be subject to allosteric regulation.



Desmocollins form a distinct subset of the cadherin family of cell adhesion molecules.

A comparison of the amino acid sequences of desmocollin, desmoglein, and the cadherins shows that although these intercellular junctional adhesion molecules share a consensus sequence in their adhesive domains that defines them as a family, several features, including the divergence in the sequence of their cytoplasmic tails, divide them into three distinct subtypes.

Desmosomal Cadherin Binding Domains of Plakoglobin (*)

To understand the reciprocal regulation between desmosomal cadherins (desmoglein and desmocollin) and plakoglobin, this work has sought to identify the binding domains involved in the formation of these protein complexes.

The desmoplakin carboxyl terminus coaligns with and specifically disrupts intermediate filament networks when expressed in cultured cells

A role for the DP carboxyl terminus in the attachment of IF to the desmosome in either a direct or indirect manner is suggested.

Two-hybrid Analysis Reveals Fundamental Differences in Direct Interactions between Desmoplakin and Cell Type-specific Intermediate Filaments*

The results of yeast two-hybrid and in vitro dot blot assays indicate that DP interacts directly with different IF types in specific ways.

Making a connection: direct binding between keratin intermediate filaments and desmosomal proteins

It is shown that the carboxy terminal "tail" of DPI associates directly with the amino terminal "head" of type II epidermal keratins, including K1, K2, K5, and K6, and this finding might have important implications for understanding a recent point mutation found within this binding site in a family with a blistering skin disorder.

Band 6 protein, a major constituent of desmosomes from stratified epithelia, is a novel member of the armadillo multigene family.

The predicted amino acid sequence of human B6P shows strong sequence homology with a murine p120 protein, which is a substrate of protein tyrosine kinase receptors and of p60v-src, and raises the question of whether the structural proteins B 6P, plakoglobin, beta-catenin and armadillo share some function.

Identification of desmoglein, a constitutive desmosomal glycoprotein, as a member of the cadherin family of cell adhesion molecules.

It is concluded that desmoglein is a member of the cadherin family of cell adhesion glycoproteins which is characterized by an unusually long cytoplasmic domain which exceeds those of the Cadherins by more than 275 amino acids, contains special repetitive elements and spans the desmosomal plaque at least once.