TitleRational Design of Protein-Specific Folding Modifiers.
Publication TypeJournal Article
Year of Publication2021
AuthorsDas 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
JournalJ Am Chem Soc
Date Published2021 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 JournalJ Am Chem Soc
PubMed ID34724378