Completion of the Vimentin Rod Domain Structure Using Experimental Restraints: A New Tool for Exploring Intermediate Filament Assembly and Mutations

David D. Gae, Madhu S. Budamagunta, John F. Hess, Robert M. McCarrick, Gary A. Lorigan, Paul G. FitzGerald, John C. Voss

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 languageEnglish (US)
Pages (from-to)1547-1560.e4
JournalStructure
Volume27
Issue number10
DOIs
StatePublished - 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

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