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.
Kang, Hyunook, et al. "Structure of the Intermediate Filament-Binding Region of Desmoplakin." PLoS ONE, vol. 11, no. 1, Jan. 2016. https://doi.org/10.1371/journal.pone.0147641
Kang, Hyunook, Weiss, Thomas M., Bang, Injin, Weis, William I., Choi, Hee -Jung, & Kursula, Petri (2016). Structure of the Intermediate Filament-Binding Region of Desmoplakin. PLoS ONE, 11(1). https://doi.org/10.1371/journal.pone.0147641
Kang, Hyunook, Weiss, Thomas M., Bang, Injin, et al., "Structure of the Intermediate Filament-Binding Region of Desmoplakin," PLoS ONE 11, no. 1 (2016), https://doi.org/10.1371/journal.pone.0147641
@article{osti_1376850,
author = {Kang, Hyunook and Weiss, Thomas M. and Bang, Injin and Weis, William I. and Choi, Hee -Jung and Kursula, Petri},
title = {Structure of the Intermediate Filament-Binding Region of Desmoplakin},
annote = {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},
url = {https://www.osti.gov/biblio/1376850},
journal = {PLoS ONE},
issn = {ISSN 1932-6203},
number = {1},
volume = {11},
place = {United States},
publisher = {Public Library of Science},
year = {2016},
month = {01}}