Journal of the American Chemical Society · 2008 · 98 citations · 28 references
Life SciencesBiochemistryBiophysicsProtein BiochemistryProtein FoldingStructural BiologyFolding KineticsMacromolecular FoldingMacromolecular StructureMolecular CrowdingProtein DynamicsProtein StructureEquilibriumMacromolecular Crowding ThermodynamicsMolecular Crowding EffectsProtein Crowding EffectsProtein Folding StabilityProtein StabilityResidue-residue InteractionsStabilization
Theory predicts that macromolecular crowding affects protein behavior, but experimental confirmation is scant. Herein, we report the first residue-level interrogation of the effects of macromolecular crowding on protein stability. We observe up to a 100-fold increase in the stability, as measured by the equilibrium constant for folding, for the globular protein chymotrypsin inhibitor 2 (CI2) in concentrations of the cosolute poly(vinylpyrrolidone) (PVP) that mimic the protein concentration in cells. We show that the increased stability is caused by the polymeric nature of PVP and that the degree of stabilization depends on both the location of the individual residue in the protein structure and the PVP concentration. Our data reinforce the assertion that macromolecular crowding stabilizes the protein by destabilizing its unfolded states.
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Primary structure effects on peptide group hydrogen exchange
Yawen Bai, John Milne, Leland Mayne et al. · Proteins Structure Function and Bioinformatics · 1993 · 1.9K citations
Protein Folding Intermediates: Native-State Hydrogen Exchange
Yawen Bai, Tobin R. Sosnick, Leland Mayne et al. · Science · 1995 · 999 citations