Transiently structured head domains control intermediate filament assembly
Open Access
- 15 February 2021
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 118 (8)
- https://doi.org/10.1073/pnas.2022121118
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.Keywords
Funding Information
- HHS | NIH | National Institute of General Medical Sciences (5R35GM130358)
This publication has 66 references indexed in Scilit:
- Desminopathies: pathology and mechanismsActa Neuropathologica, 2012
- Cell-free Formation of RNA Granules: Bound RNAs Identify Features and Components of Cellular AssembliesCell, 2012
- Antiparallel β-sheet architecture in Iowa-mutant β-amyloid fibrilsProceedings of the National Academy of Sciences of the United States of America, 2012
- RNA Binding Proteins Accumulate at the Postsynaptic Density with Synaptic ActivityJournal of Neuroscience, 2012
- P granules extend the nuclear pore complex environment in the C. elegans germ lineThe Journal of cell biology, 2011
- Detection of a Transient Intermediate in a Rapid Protein Folding Process by Solid-State Nuclear Magnetic ResonanceJournal of the American Chemical Society, 2009
- Natively Unfolded Nucleoporins Gate Protein Diffusion across the Nuclear Pore ComplexCell, 2007
- Solid State NMR Reveals a pH-dependent Antiparallel β-Sheet Registry in Fibrils Formed by a β-Amyloid PeptideJournal of Molecular Biology, 2004
- Assembly properties of dominant and recessive mutations in the small mouse neurofilament (NF-L) subunit.The Journal of cell biology, 1990
- Fixed point theory of iterative excitation schemes in NMRThe Journal of Chemical Physics, 1985