Direct Observation of the Three-State Folding of a Single Protein Molecule

@article{Cecconi2005DirectOO,
  title={Direct Observation of the Three-State Folding of a Single Protein Molecule},
  author={Ciro Cecconi and Elizabeth Anne Shank and Carlos J. Bustamante and Susan Marqusee},
  journal={Science},
  year={2005},
  volume={309},
  pages={2057 - 2060}
}
We used force-measuring optical tweezers to induce complete mechanical unfolding and refolding of individual Escherichia coli ribonuclease H (RNase H) molecules. The protein unfolds in a two-state manner and refolds through an intermediate that correlates with the transient molten globule–like intermediate observed in bulk studies. This intermediate displays unusual mechanical compliance and unfolds at substantially lower forces than the native state. In a narrow range of forces, the molecule… 
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