Rational Design of Protein-Specific Folding Modifiers.
|Title||Rational Design of Protein-Specific Folding Modifiers.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Das A, Yadav A, Gupta M, R P, Terse VL, Vishvakarma V, Singh S, Nandi T, Banerjee A, Mandal K, Gosavi S, Das R, Ainavarapu SRama Koti, Maiti S|
|Journal||J Am Chem Soc|
|Date Published||2021 Nov 01|
Protein-folding can go wrong and , with significant consequences for the living organism and the pharmaceutical industry, respectively. Here we propose a design principle for small-peptide-based protein-specific folding modifiers. The principle is based on constructing a "xenonucleus", which is a prefolded peptide that mimics the folding nucleus of a protein. Using stopped-flow kinetics, NMR spectroscopy, Förster resonance energy transfer, single-molecule force measurements, and molecular dynamics simulations, we demonstrate that a xenonucleus can make the refolding of ubiquitin faster by 33 ± 5%, while variants of the same peptide have little or no effect. Our approach provides a novel method for constructing specific, genetically encodable folding catalysts for suitable proteins that have a well-defined contiguous folding nucleus.
|Alternate Journal||J Am Chem Soc|