Apr 29, 2020

Rational design of protein-specific folding modifiers

BioRxiv : the Preprint Server for Biology
A. DasSudipta Maiti

Abstract

Protein folding can go wrong in vivo and in vitro, with significant consequences for the living cell and the pharmaceutical industry, respectively. Here we propose a general design principle for constructing small peptide-based protein-specific folding modifiers. We construct a xenonucleus, which is a pre-folded peptide that resembles the folding nucleus of a protein, and demonstrate its activity on the folding of ubiquitin. Using stopped-flow kinetics, NMR spectroscopy, Forster Resonance Energy transfer, single-molecule force measurements, and molecular dynamics simulations, we show that the ubiquitin xenonucleus can act as an effective decoy for the native folding nucleus. It can make the refolding faster by 33 +/- 5% at 3 M GdnHCl. In principle, our approach provides a general method for constructing specific, genetically encodable, folding modifiers for any protein which has a well-defined contiguous folding nucleus.

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Mentioned in this Paper

4-Amino-N, N-diethylaniline sulfate
RNA Polymerase II
Toxic Shock Syndrome
Conserved Sequence
Nucleosomes
Patterns
Transcription Initiation Site
Cytopathogenic Effect, Viral
Transcription, Genetic
Ac-Nle-c(Asp-Cpe-DNal(2')-Arg-Trp-Lys)-NH2

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