Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 8, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2022121118
Keywords
low complexity domains; intermediate filaments; phase separation; labile cross-beta structures; in situ structural analysis
Categories
Funding
- NIH [1S10OD021685-01A1]
- National Institute of General Medical Sciences [5R35GM130358]
- Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Ask authors/readers for more resources
Low complexity head domains of neurofilament light and desmin intermediate filaments can switch between conformational disorder and beta-strand-enriched polymers. Solid-state NMR studies reveal spectral patterns consistent with structural order, and phosphorylation and disease-causing mutations can alter self-association of these domains. The facultative structural assembly via labile, beta-strand-enriched self-interactions may broadly influence cell morphology.
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, beta-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 beta-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, beta-strand-enriched self-interactions may broadly influence cell morphology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available