The Knotted Protein UCH-L1 Exhibits Partially Unfolded Forms under Native Conditions that Share Common Structural Features with Its Kinetic Folding Intermediates.

@article{Lou2016TheKP,
  title={The Knotted Protein UCH-L1 Exhibits Partially Unfolded Forms under Native Conditions that Share Common Structural Features with Its Kinetic Folding Intermediates.},
  author={Shih-Chi Lou and Svava K Wetzel and Hongyu Zhang and Elizabeth W Crone and Yun-Tzai Lee and Sophie E. Jackson and Shang-Te Danny Hsu},
  journal={Journal of molecular biology},
  year={2016},
  volume={428 11},
  pages={
          2507-2520
        }
}
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34 Citations
Background Citations
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Methods Citations
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Results Citations
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34 Citations

Characterization of the Folding of a 52-Knotted Protein Using Engineered Single-Tryptophan Variants.
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TLDR
It is shown that the catalytic domain of UCH-L5 exhibits higher equilibrium folding stability with an unfolding rate on the scale of 10−8 s−1, over four orders of magnitudes slower than its paralogs, namely UCH- L1 and -L3, which have shorter cross-over loops.
The exclusive effects of chaperonin on the behavior of proteins with 52 knot
TLDR
The results of the work show that the crowded environment of the cell should have a positive effect on the kinetics of complex knotted proteins, especially when proteins with deeper knots are found in this family.
Folding analysis of the most complex Stevedore’s protein knot
TLDR
The authors' multiparametric folding analyses suggest that DehI unfolds through a linear folding pathway with two distinct folding intermediates by initial hydrophobic collapse followed by nucleation condensation, and that knotting precedes the formation of secondary structures.
Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease
TLDR
The results revealed unprecedentedly slow kinetics of ClpXP-mediated proteolysis for the proteasome-associated UCHL5: ten thousand times slower than that of a green fluorescence protein (GFP), which has a comparable size to the UCH domain but much higher chemical and thermal stabilities.
Cross-over loop cysteine C152 acts as an antioxidant to maintain the folding stability and deubiquitinase activity of UCH-L1 under oxidative stress.
The AAA+ protease ClpXP can easily degrade a 31 and a 52-knotted protein
TLDR
The results are consistent with mechanisms in which either the knot simply slips along the polypeptide chain and falls off the free terminus, or one in which the tightened knot enters the translocation pore of ClpXP.
Binding-induced folding under unfolding conditions: Switching between induced fit and conformational selection mechanisms
TLDR
The results indicate that, in the case of intrinsically disordered proteins too, the folding mechanism is determined by the concentration of the ligand that induces structure formation.
Protein knotting through concatenation significantly reduces folding stability
  • S. Hsu
  • Chemistry
    Scientific reports
  • 2016
TLDR
The results suggested that the design strategy of protein knotting by concatenation may be thermodynamically unfavourable due to covalent constrains imposed on the flexible fraying ends of the template structure, leading to rugged free energy landscape with increased propensity to form off-pathway folding intermediates.
Converging experimental and computational views of the knotting mechanism of a small knotted protein.
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