Protein melt temp/half life relation?

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SUMMARY

The discussion centers on the relationship between protein melt temperature (Tm) and half-life, particularly in the context of thermal instability. Participants highlight that while the ubiquitin-proteasome pathway typically regulates protein degradation, there is a hypothesis that thermal instability may influence the half-life of proteins lacking degradation tags. The inquiry seeks to establish a mathematical model linking Tm to half-life, emphasizing the need for empirical or theoretical references to support this correlation.

PREREQUISITES
  • Understanding of protein thermodynamics and stability
  • Familiarity with the ubiquitin-proteasome pathway
  • Knowledge of synthetic biology concepts, particularly degron tags
  • Experience with mathematical modeling in biological systems
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  • Research the correlation between protein melt temperature and half-life in thermally unstable proteins
  • Explore empirical studies on protein degradation mechanisms beyond the ubiquitin-proteasome pathway
  • Investigate mathematical modeling techniques for predicting protein stability and degradation
  • Review literature on thermodynamic stability and its impact on protein function and lifespan
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Researchers in molecular biology, synthetic biologists, and biochemists interested in protein stability, degradation mechanisms, and mathematical modeling of biological processes.

primu019
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Is anyone familiar with a way to determine the half-life of a protein from its melt temperature (Tm)? It seems like there ought to be some sort of correlation, be it theoretical or empirical.
 
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In many cases, protein degradation is not related to the thermodynamic stability of the protein, but rather, degradation is a regulated biological process that occurs through the ubiquitin-proteosome pathway. In this way, the cell can control the half-lives of proteins based on their biological functions and alter protein half-lives in different cell types and under different cellular conditions.
 
True. However, I am specifically inquiring about degradation when this is not the case. For the ubiquitin-proteasome pathway, there is usually an identifiable marker--what we call a 'degron tag' (I am coming from synthetic biology background here), and results in a half-life on the scale of minutes. In the case where I include no degradation tag for ubiquitin-mediated degradation, I am assuming the degradation must be a result of thermal instability. The classes of proteins I speak of here have half-lives on the scale of hours. I am hoping to refine this further for a mathematical model I am building. I have published information on the melt temp, and am hoping to work this back to half-life in some way. Thanks for the reply. Any further insight would be appreciated as well.
 
primu019 said:
I am assuming the degradation must be a result of thermal instability.
This sounds more like a thermodynamics question, but I cannot find good references. Could you please indicate how you made that assumption? Clearly I am missing something.
 
According to my colleagues with 30+ years of molecular biology experience, if a protein is not tagged for proteasome-mediated degradation, it degrades due to thermal instability. If this is true, there must be some relation between melt temperature and half-life. My hope in posting this is that someone might be aware of a reference that describes this relation, or that someone can correct an error in my thought process and explain why a relation or correlation does not exist.
 
ttt
 

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