Abstract
In vitro folding studies of several proteins revealed the formation, within 2–4 msec, of transient intermediates with a large far-UV ellipticity but no amide proton protection. To solve the contradiction between the secondary structure contents estimated by these two methods, we characterized the isolated C-terminal fragment F2 of the tryptophan synthase β2 subunit. In β2, F2 forms its tertiary interactions with the F1 N-terminal region. Hence, in the absence of F1, isolated F2 should remain at an early folding stage with no long-range interactions. We shall show that isolated F2 folds into, and remains in, a “state” called the pre-molten globule, that indeed corresponds to a 2- to 4-msec intermediate. This condensed, but not compact, “state” corresponds to an array of conformations in rapid equilibrium comprising native as well as nonnative secondary structures. It fits the “new view” on the folding process.
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Chaffotte, A.F., Guijarro, J.I., Guillou, Y. et al. The “Pre-Molten Globule,” a New Intermediate in Protein Folding. J Protein Chem 16, 433–439 (1997). https://doi.org/10.1023/A:1026397008011
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DOI: https://doi.org/10.1023/A:1026397008011