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X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
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X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050

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Trimethylamine-N-oxide modulates the reductive unfolding of onconase

Robert F Gahl1, Mahesh Narayan, Guoqiang Xu

  • 1Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA.

Biochemical and Biophysical Research Communications
|November 16, 2004
PubMed

Insights

Trimethylamine-N-oxide (TMAO) slows protein unfolding by altering local structures, not overall stability. This study reveals TMAO’s impact on redox-dependent protein dynamics and folding.

Area of Science:

  • Biochemistry and Molecular Biology
  • Protein Dynamics and Stability

Background:

  • Trimethylamine-N-oxide (TMAO) is a physiological osmolyte known to stabilize proteins.
  • TMAO's stabilizing mechanism involves decreasing the entropy of the unfolded state via a solvophobic effect.
  • Understanding TMAO's influence on protein unfolding dynamics is crucial for protein folding research.

Purpose of the Study:

  • To investigate the effect of TMAO on the reductive unfolding of onconase (ONC).
  • To determine if TMAO affects the rate and/or stability of ONC during reductive unfolding.
  • To provide direct evidence for TMAO-induced local structural changes influencing protein unfolding.

Main Methods:

  • Studied the reductive unfolding of onconase (ONC) in the presence of TMAO.
  • Analyzed the formation of the reductive intermediate, des [30-75].
  • Assessed the impact of TMAO on protein unfolding rates and native protein stability.

Main Results:

  • TMAO significantly diminishes the reductive unfolding rate of onconase.
  • TMAO does not substantially alter the stability of native onconase relative to its denatured state.
  • Evidence suggests TMAO induces local structural changes that impede redox-dependent unfolding.

Conclusions:

  • TMAO's effect on protein unfolding is mediated by local structural modifications.
  • The findings highlight TMAO's role in modulating the kinetics of redox-dependent protein unfolding.
  • Implications for understanding protein folding and unfolding mechanisms are discussed.

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