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Determine how the presence of dry molten globule intermediates during protein unfolding challenges the traditional two-state folding paradigm.

June 15, 2010Proteins Structure Function and BioinformaticsOpen Access

Dry molten globule intermediates and the mechanism of protein unfolding

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Determine how the presence of dry molten globule intermediates during protein unfolding challenges the traditional two-state folding paradigm.
Evaluated folding and unfolding structural data across four unrelated model proteins.
Assessed amide proton protection, side-chain packing, and secondary structure compaction in dry molten globule states.
Modeled free-energy barrier transitions and analyzed phi-value mechanisms derived from Brønsted-Leffler plots.
Demonstrated that four unrelated proteins form a dry molten globule as the initial unfolding intermediate, unlocking side chains while preserving intact backbone structure and excluding solvent.
Showed that the primary free-energy barrier separating unfolded and native states occurs during the transition between the unfolded state and the dry molten globule.
Established that phi-values reflect local backbone structure rather than specific side-chain packing interactions, leading to the breakdown of conventional two-state folding models.

Authors

RBRobert L. BaldwinOntario Institute for Cancer Research CFCarl FriedenWashington University in St. Louis GRGeorge D. RoseJohns Hopkins University

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Implication

Biophysical analysis demonstrates dry molten globule intermediate formation during protein unfolding, indicating that conventional two-state folding models fail to capture discrete structural...

Cite This Study

Baldwin et al. (2010) studied this question.

synapsesocial.com/papers/6a852c57e1eabc68e2928d82 https://doi.org/10.1002/prot.22803

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Implication

Biophysical analysis demonstrates dry molten globule intermediate formation during protein unfolding, indicating that conventional two-state folding models fail to capture discrete structural...

Dry molten globule intermediates and the mechanism of protein unfolding

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Discussion

Implication

Cite This Study

Dry molten globule intermediates and the mechanism of protein unfolding

Key Points

Discussion

Implication

Cite This Study