Ligand-promoted protein folding by biased kinetic partitioning

February 20th, 2017 by Karan S Hingorani

Nature Chemical Biology 13, 369 (2017). doi:10.1038/nchembio.2303

Authors: Karan S Hingorani, Matthew C Metcalf, Derrick T Deming, Scott C Garman, Evan T Powers & Lila M Gierasch

Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems.