skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structure of the Intermediate Filament-Binding Region of Desmoplakin

Abstract

Here, desmoplakin (DP) is a cytoskeletal linker protein that connects the desmosomal cadherin/plakoglobin/plakophilin complex to intermediate filaments (IFs). The C-terminal region of DP (DPCT) mediates IF binding, and contains three plakin repeat domains (PRDs), termed PRD-A, PRD-B and PRD-C. Previous crystal structures of PRDs B and C revealed that each is formed by 4.5 copies of a plakin repeat (PR) and has a conserved positively charged groove on its surface. Although PRDs A and B are linked by just four amino acids, B and C are separated by a 154 residue flexible linker, which has hindered crystallographic analysis of the full DPCT. Here we present the crystal structure of a DPCT fragment spanning PRDs A and B, and elucidate the overall architecture of DPCT by small angle X-ray scattering (SAXS) analysis. The structure of PRD-A is similar to that of PRD-B, and the two domains are arranged in a quasi-linear arrangement, and separated by a 4 amino acid linker. Analysis of the B-C linker region using secondary structure prediction and the crystal structure of a homologous linker from the cytolinker periplakin suggests that the N-terminal ~100 amino acids of the linker form two PR-like motifs. SAXS analysis of DPCT indicatesmore » an elongated but non-linear shape with R g = 51.5 Å and D max = 178 Å. These data provide the first structural insights into an IF binding protein containing multiple PRDs and provide a foundation for studying the molecular basis of DP-IF interactions.« less

Authors:
 [1];  [2];  [1];  [3];  [1];  [4]
  1. Seoul National Univ., Seoul (South Korea). Dept. of Biological Sciences
  2. SLAC National Accelerator Lab., Menlo Park, CA (United States)
  3. Stanford Univ. School of Medicine, Stanford, CA (United States). Depts. of Structural Biology and Molecular & Cellular Physiology
  4. Univ. i Bergen (Norway)
Publication Date:
Research Org.:
Seoul National Univ., Seoul (South Korea). Dept. of Biological Sciences
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1376850
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; crystal structure; amino acid analysis; cytoskeletal proteins; sequence motif analysis; computer software; protein structure; small-angle scattering; vimentin

Citation Formats

Kang, Hyunook, Weiss, Thomas M., Bang, Injin, Weis, William I., Choi, Hee -Jung, and Kursula, Petri. Structure of the Intermediate Filament-Binding Region of Desmoplakin. United States: N. p., 2016. Web. doi:10.1371/journal.pone.0147641.
Kang, Hyunook, Weiss, Thomas M., Bang, Injin, Weis, William I., Choi, Hee -Jung, & Kursula, Petri. Structure of the Intermediate Filament-Binding Region of Desmoplakin. United States. doi:10.1371/journal.pone.0147641.
Kang, Hyunook, Weiss, Thomas M., Bang, Injin, Weis, William I., Choi, Hee -Jung, and Kursula, Petri. Mon . "Structure of the Intermediate Filament-Binding Region of Desmoplakin". United States. doi:10.1371/journal.pone.0147641. https://www.osti.gov/servlets/purl/1376850.
@article{osti_1376850,
title = {Structure of the Intermediate Filament-Binding Region of Desmoplakin},
author = {Kang, Hyunook and Weiss, Thomas M. and Bang, Injin and Weis, William I. and Choi, Hee -Jung and Kursula, Petri},
abstractNote = {Here, desmoplakin (DP) is a cytoskeletal linker protein that connects the desmosomal cadherin/plakoglobin/plakophilin complex to intermediate filaments (IFs). The C-terminal region of DP (DPCT) mediates IF binding, and contains three plakin repeat domains (PRDs), termed PRD-A, PRD-B and PRD-C. Previous crystal structures of PRDs B and C revealed that each is formed by 4.5 copies of a plakin repeat (PR) and has a conserved positively charged groove on its surface. Although PRDs A and B are linked by just four amino acids, B and C are separated by a 154 residue flexible linker, which has hindered crystallographic analysis of the full DPCT. Here we present the crystal structure of a DPCT fragment spanning PRDs A and B, and elucidate the overall architecture of DPCT by small angle X-ray scattering (SAXS) analysis. The structure of PRD-A is similar to that of PRD-B, and the two domains are arranged in a quasi-linear arrangement, and separated by a 4 amino acid linker. Analysis of the B-C linker region using secondary structure prediction and the crystal structure of a homologous linker from the cytolinker periplakin suggests that the N-terminal ~100 amino acids of the linker form two PR-like motifs. SAXS analysis of DPCT indicates an elongated but non-linear shape with Rg = 51.5 Å and Dmax = 178 Å. These data provide the first structural insights into an IF binding protein containing multiple PRDs and provide a foundation for studying the molecular basis of DP-IF interactions.},
doi = {10.1371/journal.pone.0147641},
journal = {PLoS ONE},
number = 1,
volume = 11,
place = {United States},
year = {2016},
month = {1}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 4 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

GNOM – a program package for small-angle scattering data processing
journal, October 1991


Uniqueness of ab initio shape determination in small-angle scattering
journal, April 2003

  • Volkov, Vladimir V.; Svergun, Dmitri I.
  • Journal of Applied Crystallography, Vol. 36, Issue 3, p. 860-864
  • DOI: 10.1107/S0021889803000268

CRYSOL – a Program to Evaluate X-ray Solution Scattering of Biological Macromolecules from Atomic Coordinates
journal, December 1995

  • Svergun, D.; Barberato, C.; Koch, M. H. J.
  • Journal of Applied Crystallography, Vol. 28, Issue 6
  • DOI: 10.1107/S0021889895007047

MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

  • Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
  • DOI: 10.1107/S0907444909042073

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

PRIMUS: a Windows PC-based system for small-angle scattering data analysis
journal, September 2003

  • Konarev, Petr V.; Volkov, Vladimir V.; Sokolova, Anna V.
  • Journal of Applied Crystallography, Vol. 36, Issue 5, p. 1277-1282
  • DOI: 10.1107/S0021889803012779

New developments in the ATSAS program package for small-angle scattering data analysis
journal, March 2012

  • Petoukhov, Maxim V.; Franke, Daniel; Shkumatov, Alexander V.
  • Journal of Applied Crystallography, Vol. 45, Issue 2
  • DOI: 10.1107/S0021889812007662

NADPH oxidase activator p67phox behaves in solution as a multidomain protein with semi-flexible linkers
journal, January 2010

  • Durand, Dominique; Vivès, Corinne; Cannella, Dominique
  • Journal of Structural Biology, Vol. 169, Issue 1
  • DOI: 10.1016/j.jsb.2009.08.009

Small-angle scattering studies of biological macromolecules in solution
journal, September 2003


PHENIX : building new software for automated crystallographic structure determination
journal, October 2002

  • Adams, Paul D.; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei
  • Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 11
  • DOI: 10.1107/S0907444902016657

X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution
journal, August 2007

  • Putnam, Christopher D.; Hammel, Michal; Hura, Greg L.
  • Quarterly Reviews of Biophysics, Vol. 40, Issue 3
  • DOI: 10.1017/S0033583507004635

JPred4: a protein secondary structure prediction server
journal, April 2015

  • Drozdetskiy, Alexey; Cole, Christian; Procter, James
  • Nucleic Acids Research, Vol. 43, Issue W1
  • DOI: 10.1093/nar/gkv332

Small-angle scattering for structural biology-Expanding the frontier while avoiding the pitfalls
journal, January 2010

  • Jacques, David A.; Trewhella, Jill
  • Protein Science, Vol. 19, Issue 4
  • DOI: 10.1002/pro.351

Scaling and assessment of data quality
journal, December 2005

  • Evans, Philip
  • Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1, p. 72-82
  • DOI: 10.1107/S0907444905036693

Sequence and structure-based prediction of eukaryotic protein phosphorylation sites
journal, December 1999

  • Blom, Nikolaj; Gammeltoft, Steen; Brunak, Søren
  • Journal of Molecular Biology, Vol. 294, Issue 5
  • DOI: 10.1006/jmbi.1999.3310

Determination of Domain Structure of Proteins from X-Ray Solution Scattering
journal, June 2001


Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206