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

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
 [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:
Accepted Manuscript
Journal Name:
Additional Journal Information:
Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 1932-6203
Public Library of Science
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)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; crystal structure; amino acid analysis; cytoskeletal proteins; sequence motif analysis; computer software; protein structure; small-angle scattering; vimentin
OSTI Identifier: