Transiently structured head domains control intermediate filament assembly.
in situ structural analysis
intermediate filaments
labile cross-β structures
low complexity domains
phase separation
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
23 02 2021
23 02 2021
Historique:
entrez:
17
2
2021
pubmed:
18
2
2021
medline:
3
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33593918
pii: 2022121118
doi: 10.1073/pnas.2022121118
pmc: PMC7923618
pii:
doi:
Substances chimiques
Desmin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM130358
Pays : United States
Organisme : NIH HHS
ID : S10 OD021684
Pays : United States
Organisme : NIH HHS
ID : S10 OD021685
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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