Transiently structured head domains control intermediate filament assembly

Xiaoming Zhou, Yi Lin, Glen Liszczak, Vasily Sysoev, Lillian Sutherland, Eiichiro Mori, Dylan Murray, Masato Kato, Robert Tycko, Steven L. McKnight

Research output: Contribution to journalArticlepeer-review

Abstract

Low complexity (LC) head domains 92 and 108 residues in length are, respectfully, required for assembly of neurofilament light (NFL) and desmin intermediate filaments (IFs). As studied in isolation, these IF head domains interconvert between states of conformational disorder and labile, βstrand-enriched polymers. Solid state nuclear magnetic resonance (ss-NMR) spectroscopic studies of NFL and desmin head domain polymers reveal spectral patterns consistent with structural order. A combination of intein chemistry and segmental isotope labeling allowed preparation of fully assembled NFL and desmin IFs that could also be studied by ss-NMR. Assembled IFs revealed spectra overlapping with those observed for β-strand-enriched polymers formed from the isolated NFL and desmin head domains. Phosphorylation and disease causing mutations reciprocally alter NFL and desmin head domain self-association, yet commonly impede IF assembly. These observations show how facultative structural assembly of LC domains via labile, β-strand-enriched self-interactions may broadly influence cell morphology.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Mar 29 2020

Keywords

  • Dynamic cellular assemblies
  • Human genetic mutations
  • In situ structural analysis
  • Intermediate filaments
  • Intrinsically disordered proteins
  • Labile cross-β structures
  • Low complexity domains
  • Phase separation
  • Segmental isotope labeling
  • Solid state NMR

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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