Association of Partially-folded Intermediates of Staphylococcal Nuclease Induces Structure and Stability
Document Type
Article
Publication Date
1999
Digital Object Identifier (DOI)
https://doi.org/10.1110/ps.8.1.161
Abstract
Staphylococcal nuclease forms three different partially-folded intermediates at low pH in the presence of low to moderate concentration of anions, differing in the amount of secondary structure, globularity, stability, and compactness. Although these intermediates are monomeric at low protein concentration (≤0.25 mg/mL), increasing concentrations of protein result in the formation of dimers and soluble oligomers, ultimately leading to larger insoluble aggregates. Unexpectedly, increasing protein concentration not only led to association, but also to increased structure of the intermediates. The secondary structure, stability, and globularity of the two less-ordered partially-folded intermediates (A1 and A2) were substantially increased upon association, suggesting that aggregation induces structure. An excellent correlation was found between degree of association and amount of structure measured by different techniques, including circular dichroism, fluorescence, Fourier transform infrared spectroscopy (FTIR), and small-angle X-ray scattering. The associated states were also substantially more stable toward urea denaturation than the monomeric forms. A mechanism is proposed, in which the observed association of monomeric intermediates involves intermolecular interactions which correspond to those found intramolecularly in normal folding to the native state.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Protein Science, v. 8, issue 1, p. 161-173
Scholar Commons Citation
Uversky, Vladimir N.; Karnoup, Anton S.; Khurana, Ritu; Segel, Daniel J.; Doniach, Sebastian; and Fink, Anthony L., "Association of Partially-folded Intermediates of Staphylococcal Nuclease Induces Structure and Stability" (1999). Molecular Medicine Faculty Publications. 650.
https://digitalcommons.usf.edu/mme_facpub/650
