Transiently structured head domains control intermediate filament assembly

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Low complexity (LC) head domains 92 and 108 residues in length are, respectively, 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, β-strand–enriched polymers. Solid-state NMR (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)
Article numbere2022121118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number8
DOIs
StatePublished - Feb 23 2021

Keywords

  • In situ structural analysis
  • Intermediate filaments
  • Labile cross-β structures
  • Low complexity domains
  • Phase separation

ASJC Scopus subject areas

  • General

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