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Ligand-promoted protein folding by biased kinetic partitioning.


ABSTRACT: 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.

SUBMITTER: Hingorani KS 

PROVIDER: S-EPMC5362304 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Ligand-promoted protein folding by biased kinetic partitioning.

Hingorani Karan S KS   Metcalf Matthew C MC   Deming Derrick T DT   Garman Scott C SC   Powers Evan T ET   Gierasch Lila M LM  

Nature chemical biology 20170220 4


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  ...[more]

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