Binding of the periplakin linker requires vimentin acidic residues D176 and E187

Commun Biol. 2020 Feb 21;3(1):83. doi: 10.1038/s42003-020-0810-y.

Abstract

Plakin proteins form connections that link the cell membrane to the intermediate filament cytoskeleton. Their interactions are mediated by a highly conserved linker domain through an unresolved mechanism. Here analysis of the human periplakin linker domain structure reveals a bi-lobed module transected by an electropositive groove. Key basic residues within the periplakin groove are vital for co-localization with vimentin in human cells and compromise direct binding which also requires acidic residues D176 and E187 in vimentin. We propose a model whereby basic periplakin linker domain residues recognize acidic vimentin side chains and form a complementary binding groove. The model is shared amongst diverse linker domains and can be used to investigate the effects of pathogenic mutations in the desmoplakin linker associated with arrhythmogenic right ventricular cardiomyopathy. Linker modules either act solely or collaborate with adjacent plakin repeat domains to create strong and adaptable tethering within epithelia and cardiac muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids, Acidic / chemistry
  • Amino Acids, Acidic / genetics
  • Amino Acids, Acidic / metabolism
  • Aspartic Acid / metabolism
  • Glutamic Acid / metabolism
  • HeLa Cells
  • Humans
  • Intermediate Filaments / chemistry
  • Intermediate Filaments / metabolism
  • Models, Molecular
  • Mutation, Missense
  • Plakins / chemistry*
  • Plakins / genetics
  • Plakins / metabolism*
  • Protein Binding / genetics
  • Protein Interaction Domains and Motifs / genetics
  • Protein Structure, Quaternary
  • Vimentin / chemistry*
  • Vimentin / genetics
  • Vimentin / metabolism*

Substances

  • Amino Acids, Acidic
  • PPL protein, human
  • Plakins
  • Vimentin
  • Aspartic Acid
  • Glutamic Acid