Polymer scaling laws of unfolded and intrinsically disordered proteins quantified with single-molecule spectroscopy
The dimensions of unfolded and intrinsically disordered proteins are highly dependent on their amino acid composition and solution conditions, especially salt and denaturant concentration. However, the quantitative implications of this behavior have remained unclear, largely because the effective th...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 40; pp. 16155 - 16160 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
02.10.2012
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | The dimensions of unfolded and intrinsically disordered proteins are highly dependent on their amino acid composition and solution conditions, especially salt and denaturant concentration. However, the quantitative implications of this behavior have remained unclear, largely because the effective theta-state, the central reference point for the underlying polymer collapse transition, has eluded experimental determination. Here, we used single-molecule fluorescence spectroscopy and two-focus correlation spectroscopy to determine the theta points for six different proteins. While the scaling exponents of all proteins converge to 0.62 ± 0.03 at high denaturant concentrations, as expected for a polymer in good solvent, the scaling regime in water strongly depends on sequence composition. The resulting average scaling exponent of 0.46 ± 0.05 for the four foldable protein sequences in our study suggests that the aqueous cellular milieu is close to effective theta conditions for unfolded proteins. In contrast, two intrinsically disordered proteins do not reach the Θ-point under any of our solvent conditions, which may reflect the optimization of their expanded state for the interactions with cellular partners. Sequence analyses based on our results imply that foldable sequences with more compact unfolded states are a more recent result of protein evolution. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: H.H. and B.S. designed research; H.H. and K.G. performed research; H.H., A.S., A.B., K.G., and D.N. contributed new reagents/analytic tools; H.H., A.S., K.G., and D.N. analyzed data; and H.H. and B.S. wrote the paper. Edited by Ken A. Dill, Stony Brook University, Stony Brook, NY, and approved August 15, 2012 (received for review May 8, 2012) |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1207719109 |