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Nat Commun. 2019 Jun 5;10(1):2453. doi: 10.1038/s41467-019-10356-0.

Disordered RNA chaperones can enhance nucleic acid folding via local charge screening.

Author information

1
Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. erik.d.holmstrom@ku.edu.
2
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045-7566, USA. erik.d.holmstrom@ku.edu.
3
Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
4
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892-0520, USA. robert.best2@nih.gov.
5
Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. schuler@bioc.uzh.ch.
6
Department of Physics, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. schuler@bioc.uzh.ch.

Abstract

RNA chaperones are proteins that aid in the folding of nucleic acids, but remarkably, many of these proteins are intrinsically disordered. How can these proteins function without a well-defined three-dimensional structure? Here, we address this question by studying the hepatitis C virus core protein, a chaperone that promotes viral genome dimerization. Using single-molecule fluorescence spectroscopy, we find that this positively charged disordered protein facilitates the formation of compact nucleic acid conformations by acting as a flexible macromolecular counterion that locally screens repulsive electrostatic interactions with an efficiency equivalent to molar salt concentrations. The resulting compaction can bias unfolded nucleic acids towards folding, resulting in faster folding kinetics. This potentially widespread mechanism is supported by molecular simulations that rationalize the experimental findings by describing the chaperone as an unstructured polyelectrolyte.

PMID:
31165735
PMCID:
PMC6549165
DOI:
10.1038/s41467-019-10356-0
[Indexed for MEDLINE]
Free PMC Article

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