Obscurin is a semi‐flexible molecule in solution

Whitley, Jacob A.; Ex‐Willey, Aidan M.; Marzolf, Daniel R.; Ackermann, Maegen A.; Tongen, Anthony L.; Kokhan, Oleksandr; Wright, Nathan T.

doi:10.1002/pro.3578

Title: Obscurin is a semi‐flexible molecule in solution

Journal Article · 05 February 2019 · Protein Science

DOI: https://doi.org/10.1002/pro.3578 · OSTI ID:1493640

Whitley, Jacob A. ^[1]; Ex‐Willey, Aidan M. ^[2]; Marzolf, Daniel R. ^[1]; Ackermann, Maegen A. ^[3]; Tongen, Anthony L. ^[4]; Kokhan, Oleksandr ^[1]; Wright, Nathan T. ^[1]

Department of Chemistry and Biochemistry James Madison University Harrisonburg Virginia, 22807
Department of Chemistry and Biochemistry James Madison University Harrisonburg Virginia, 22807, Department of Physiology and Cell Biology, Wexner Medical Center Ohio State University Columbus Ohio, 43210
Department of Physiology and Cell Biology, Wexner Medical Center Ohio State University Columbus Ohio, 43210
Department of Mathematics and Statistics James Madison University Harrisonburg Virginia, 22807

Abstract Obscurin, a giant modular cytoskeletal protein, is comprised mostly of tandem immunoglobulin‐like (Ig‐like) domains. This architecture allows obscurin to connect distal targets within the cell. The linkers connecting the Ig domains are usually short (3–4 residues). The physical effect arising from these short linkers is not known; such linkers may lead to a stiff elongated molecule or, conversely, may lead to a more compact and dynamic structure. In an effort to better understand how linkers affect obscurin flexibility, and to better understand the physical underpinnings of this flexibility, here we study the structure and dynamics of four representative sets of dual obscurin Ig domains using experimental and computational techniques. We find in all cases tested that tandem obscurin Ig domains interact at the poles of each domain and tend to stay relatively extended in solution. NMR, SAXS, and MD simulations reveal that while tandem domains are elongated, they also bend and flex significantly. By applying this behavior to a simplified model, it becomes apparent obscurin can link targets more than 200 nm away. However, as targets get further apart, obscurin begins acting as a spring and requires progressively more energy to further elongate.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1493640

Journal Information:: Protein Science, Journal Name: Protein Science Journal Issue: 4 Vol. 28; ISSN 0961-8368

Publisher:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: United Kingdom

Language:: English

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