Revealing Conformational Variants of Solution-phase Intrinsically Disordered Tau Protein at the Single-Molecule Level

Authors

Lydia H. Manger, University of Wisconsin - Madison
Alexander K. Foote, University of Wisconsin-Madison
Sharla L. Wood, University of Wisconsin-Madison
Michael R. Holden, University of Denver
Kevin D. Heylman, University of Wisconsin-Madison
Martin Margittai, University of DenverFollow
Randall H. Goldsmith, University of Wisconsin-Madison

Publication Date

11-14-2017

Document Type

Article

Organizational Units

Chemistry and Biochemistry

Keywords

Biophysics, Fluorescence spectroscopy, Microfluidics, Protein structures, Single-molecule studies

Abstract

Intrinsically disordered proteins, such as tau protein, adopt a variety of conformations in solution, complicating solution‐phase structural studies. We employed an anti‐Brownian electrokinetic (ABEL) trap to prolong measurements of single tau proteins in solution. Once trapped, we recorded the fluorescence anisotropy to investigate the diversity of conformations sampled by the single molecules. A distribution of anisotropy values obtained from trapped tau protein is conspicuously bimodal while those obtained by trapping a globular protein or individual fluorophores are not. Time‐resolved fluorescence anisotropy measurements were used to provide an explanation of the bimodal distribution as originating from a shift in the compaction of the two different families of conformations.

Publication Statement

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Recommended Citation

Manger, L. H., Foote, A. K., Wood, S. L., Holden, M. R., Heylman, K. D., Margittai, M., & Goldsmith, R. H. (2017). Revealing Conformational Variants of Solution‐Phase Intrinsically Disordered Tau Protein at the Single‐Molecule Level. Angewandte Chemie (International Ed.), 56(49), 15584-15588. DOI: 10.1002/anie.201708242.