Ligand-promoted protein folding by biased kinetic partitioning.
- Resource Type
- Academic Journal
- Authors
- Hingorani KS; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.; Department of Biochemistry &Molecular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.; Metcalf MC; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.; Department of Biochemistry &Molecular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.; Deming DT; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.; Department of Biochemistry &Molecular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.; Garman SC; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.; Department of Biochemistry &Molecular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.; Powers ET; Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA.; Gierasch LM; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.; Department of Biochemistry &Molecular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.; Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
- Source
- Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101231976 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4469 (Electronic) Linking ISSN: 15524450 NLM ISO Abbreviation: Nat Chem Biol Subsets: MEDLINE
- Subject
- Language
- English
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.