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

Nature Structural Biology volume 9, pages 612–620 (2002)Cite this article

Abstract

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 crystal structures of domains B and C. In contrast to the elongated structures formed by other kinds of repeat motifs, the plakin repeats form a globular structure with a unique fold. A conserved basic groove found on the domain may represent an IF-binding site.

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Figure 1: Domain structure of desmoplakin and binding to vimentin.
Figure 2: Structure of the DPCT domains B and C.
Figure 3: Plakin repeat structure.
Figure 4: Structure-based alignment of the plakin repeat motif.
Figure 5: Repeat packing.
Figure 6: Comparison of domains B and C.
Figure 7: A conserved basic groove on the PRD.

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Acknowledgements

We thank P. Ellis for beamline support. Portions of this research were carried out at the Stanford Synchrotron Radiation Laboratory (SSRL), a national user facility operated by Stanford University on behalf of the U.S. Department of Energy, Office of Basic Energy Sciences. The SSRL Structural Molecular Biology Program is supported by the Department of Energy, Office of Biological and Environmental Research, and by the National Institutes of Health, National Center for Research Resources, Biomedical Technology Program, and the National Institute of General Medical Sciences. H.-J.C. was supported by fellowships from the Korea Science and Engineering Foundation and the American Heart Association. This work was supported by grants to W.I.W. and K.J.G from the National Institutes of Health.

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Authors and Affiliations

  1. Departments of Structural Biology and Molecular Cellular Physiology, Stanford University School of Medicine, 299 Campus Drive West, Stanford, 94305, California, USA

    Hee-Jung Choi, Shaun Park-Snyder & William I. Weis

  2. Departments of Pathology, Dermatology and the R.H. Lurie Cancer Center, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, 60611, Illinois, USA

    Lauren T. Pascoe & Kathleen J. Green

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Correspondence to William I. Weis.

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Choi, HJ., Park-Snyder, S., Pascoe, L. et al. Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique repeat motif structure. Nat Struct Mol Biol 9, 612–620 (2002). https://doi.org/10.1038/nsb818

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