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Transiently Structured Head Domains Control Intermediate Filament Assembly

38 Pages Posted: 10 Apr 2020 Sneak Peek Status: Under Review

See all articles by Xiaoming Zhou

Xiaoming Zhou

UT Southwestern Medical Center - Department of Biochemistry

Yi Lin

UT Southwestern Medical Center - Department of Biochemistry

Glen Liszczak

UT Southwestern Medical Center - Department of Biochemistry

Vasily Sysoev

University of Texas at Dallas - Department of Biochemistry

Lillian Sutherland

University of Texas at Dallas - Department of Biochemistry

Eiichiro Mori

Nara Medical University

Dylan Murray

University of California, Davis - Department of Chemistry

Masato Kato

UT Southwestern Medical Center - Department of Biochemistry

Robert Tycko

National Institutes of Health (NIH)

Steven L. McKnight

UT Southwestern Medical Center - Department of Biochemistry

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Abstract

Low complexity (LC) head domains 92 and 108 residues in length are, respectfully, 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 nuclear magnetic resonance (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: low complexity domains, intermediate filaments, intrinsically disordered proteins, phase separation, human genetic mutations, labile cross-β structures, dynamic cellular assemblies, solid state NMR, segmental isotope labeling, in situ structural analysis.

Suggested Citation

Zhou, Xiaoming and Lin, Yi and Liszczak, Glen and Sysoev, Vasily and Sutherland, Lillian and Mori, Eiichiro and Murray, Dylan and Kato, Masato and Tycko, Robert and McKnight, Steven L., Transiently Structured Head Domains Control Intermediate Filament Assembly. Available at SSRN: https://ssrn.com/abstract=3565023 or http://dx.doi.org/10.2139/ssrn.3565023
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Xiaoming Zhou

UT Southwestern Medical Center - Department of Biochemistry ( email )

2601 North Floyd Road
Richardson, TX 75083
United States

Yi Lin

UT Southwestern Medical Center - Department of Biochemistry

2601 North Floyd Road
Richardson, TX 75083
United States

Glen Liszczak

UT Southwestern Medical Center - Department of Biochemistry ( email )

2601 North Floyd Road
Richardson, TX 75083
United States

Vasily Sysoev

University of Texas at Dallas - Department of Biochemistry ( email )

2601 North Floyd Road
Richardson, TX 75083
United States

Lillian Sutherland

University of Texas at Dallas - Department of Biochemistry ( email )

2601 North Floyd Road
Richardson, TX 75083
United States

Eiichiro Mori

Nara Medical University ( email )

Japan

Dylan Murray

University of California, Davis - Department of Chemistry ( email )

1 Shields Ave.
Davis, CA 95616
United States

Masato Kato

UT Southwestern Medical Center - Department of Biochemistry ( email )

2601 North Floyd Road
Richardson, TX 75083
United States

Robert Tycko

National Institutes of Health (NIH) ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Steven L. McKnight (Contact Author)

UT Southwestern Medical Center - Department of Biochemistry ( email )

2601 North Floyd Road
Richardson, TX 75083
United States

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