Protein melt temp/half life relation?

In summary, according to this expert, degradation of proteins is not always related to the thermodynamic stability of the protein, but rather, degradation is a regulated biological process that occurs through the ubiquitin-proteosome pathway. However, this relation cannot be determined from the data alone, and further research is needed in this area.
  • #1
primu019
5
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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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  • #2
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.
 
  • #3
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.
 
  • #4
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.
 
  • #5
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.
 
  • #6
ttt
 

1. What is protein melt temperature?

Protein melt temperature, also known as melting point, is the temperature at which a protein denatures or unfolds, losing its structure and function. This can be caused by changes in pH, temperature, or exposure to certain chemicals.

2. How is protein melt temperature determined?

Protein melt temperature is typically determined using techniques such as differential scanning calorimetry (DSC) or circular dichroism (CD). These techniques measure changes in protein structure and can identify the temperature at which denaturation occurs.

3. What factors affect protein melt temperature?

Several factors can affect protein melt temperature, including the protein's amino acid sequence, its secondary and tertiary structure, and the presence of stabilizing or destabilizing agents such as salts or detergents.

4. What is the relationship between protein melt temperature and half-life?

The relationship between protein melt temperature and half-life is complex and can vary depending on the specific protein. In general, proteins with higher melt temperatures tend to have longer half-lives, as they are more stable and less likely to denature or degrade.

5. How can knowledge of protein melt temperature and half-life be useful?

Understanding a protein's melt temperature and half-life can be useful in various fields, including drug development and biotechnology. It can help predict the stability and shelf life of proteins and guide the design of experiments and therapies involving these proteins.

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