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

doi:10.1016/j.str.2019.07.011

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 journal › Article

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)
Pages (from-to)	1547-1560.e4
Journal	Structure
Volume	27
Issue number	10
DOIs	https://doi.org/10.1016/j.str.2019.07.011
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

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Gae, D. D., Budamagunta, M. S., Hess, J. F., McCarrick, R. M., Lorigan, G. A., FitzGerald, P. G., & Voss, J. C. (2019). Completion of the Vimentin Rod Domain Structure Using Experimental Restraints: A New Tool for Exploring Intermediate Filament Assembly and Mutations. Structure, 27(10), 1547-1560.e4. https://doi.org/10.1016/j.str.2019.07.011

Completion of the Vimentin Rod Domain Structure Using Experimental Restraints : A New Tool for Exploring Intermediate Filament Assembly and Mutations. / Gae, David D.; Budamagunta, Madhu S.; Hess, John F.; McCarrick, Robert M.; Lorigan, Gary A.; FitzGerald, Paul G.; Voss, John C.

In: Structure, Vol. 27, No. 10, 01.10.2019, p. 1547-1560.e4.

Research output: Contribution to journal › Article

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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.",

keywords = "electron paramagnetic resonance, EPR, ESR, intermediate filaments, molecular dynamics, molecular modeling, site-directed spin labeling, UCSF chimera: macromolecular structure, vimentin",

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