Abstract
Electron paramagnetic resonance (EPR) spectroscopy of full-length vimentin and X-ray crystallography of vimentin peptides has provided concordant structural data for nearly the entire central rod domain of the protein. In this report, we use a combination of EPR spectroscopy and molecular modeling to determine the structure and dynamics of the missing region and unite the separate elements into a single structure. Validation of the linker 1–2 (L1-2) modeling approach is demonstrated by the close correlation between EPR and X-ray data in the previously solved regions. Importantly, molecular dynamic (MD) simulation of the constructed model agrees with spin label motion as determined by EPR. Furthermore, MD simulation shows L1-2 heterogeneity, with a concerted switching of states among the dimer chains. These data provide the first ever experimentally driven model of a complete intermediate filament rod domain, providing research tools for further modeling and assembly studies.
Original language | English (US) |
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Pages (from-to) | 1547-1560.e4 |
Journal | Structure |
Volume | 27 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2019 |
Keywords
- electron paramagnetic resonance
- EPR
- ESR
- intermediate filaments
- molecular dynamics
- molecular modeling
- site-directed spin labeling
- UCSF chimera: macromolecular structure
- vimentin
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology