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

51 Pages Posted: 7 Jan 2019 Publication Status: Published

See all articles by David D. Gae

David D. Gae

University of California, San Francisco (UCSF) - Department of Surgery

Madhu S. Budamagunta

University of California, Davis - Department of Biochemistry and Molecular Medicine

John F. Hess

University of California, Davis - Department of Cell Biology and Human Anatomy

Robert M. McCarrick

Miami University of Ohio - Department of Chemistry and Biochemistry

Gary A. Lorigan

Miami University of Ohio - Department of Chemistry and Biochemistry

Paul G. FitzGerald

University of California, Davis - Department of Cell Biology and Human Anatomy

John C. Voss

University of California, Davis - Department of Biochemistry and Molecular Medicine

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Abstract

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 L1-2 modeling approach is demonstrated by the close correlation between EPR and X-ray data in the previously solved regions. Importantly, Molecular Dynamics (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 IF rod domain, providing research tools for further modeling and assembly studies.

Suggested Citation

Gae, David D. and Budamagunta, Madhu S. and Hess, John F. and McCarrick, Robert M. and Lorigan, Gary A. and FitzGerald, Paul G. and Voss, John C., Completion of the Vimentin Rod Domain Structure Using Experimental Restraints: A New Tool for Exploring Intermediate Filament Assembly and Mutations (November 27, 2018). Available at SSRN: https://ssrn.com/abstract=3291329 or http://dx.doi.org/10.2139/ssrn.3291329
This is a paper under consideration at Cell Press and has not been peer-reviewed.

David D. Gae (Contact Author)

University of California, San Francisco (UCSF) - Department of Surgery

San Francisco, CA 94143
United States

Madhu S. Budamagunta

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

John F. Hess

University of California, Davis - Department of Cell Biology and Human Anatomy

4303 Tupper Hall
Davis, CA 95616
United States

Robert M. McCarrick

Miami University of Ohio - Department of Chemistry and Biochemistry

Oxford, OH 45056
United States

Gary A. Lorigan

Miami University of Ohio - Department of Chemistry and Biochemistry

Oxford, OH 45056
United States

Paul G. FitzGerald

University of California, Davis - Department of Cell Biology and Human Anatomy ( email )

4303 Tupper Hall
Davis, CA 95616
United States

John C. Voss

University of California, Davis - Department of Biochemistry and Molecular Medicine ( email )

One Shields Avenue
Davis, CA 95616
United States

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