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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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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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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DOI: https://doi.org/10.1038/nsb818
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