Protein melt temp/half life relation?

AI Thread Summary
The discussion centers on the relationship between a protein's melt temperature (Tm) and its half-life, particularly in cases where degradation is not mediated by the ubiquitin-proteasome pathway. The inquiry suggests that while protein degradation is often a regulated biological process, there may be instances where thermal instability plays a significant role in the degradation of proteins lacking degradation tags. The participant seeks to establish a correlation between Tm and half-life for proteins with half-lives on the order of hours, aiming to refine a mathematical model. They express a need for references or insights that could clarify whether such a relationship exists or if their assumptions about thermal instability and degradation are flawed. The discussion highlights a gap in available literature regarding the theoretical or empirical connections between these two parameters.
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
 
https://www.discovermagazine.com/the-deadliest-spider-in-the-world-ends-lives-in-hours-but-its-venom-may-inspire-medical-miracles-48107 https://en.wikipedia.org/wiki/Versutoxin#Mechanism_behind_Neurotoxic_Properties https://www.sciencedirect.com/science/article/abs/pii/S0028390817301557 (subscription or purchase requred) The structure of versutoxin (δ-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel...
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