Protein melt temp/half life relation?

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Discussion Overview

The discussion centers around the relationship between the melt temperature (Tm) of proteins and their half-lives, exploring whether a correlation exists between these two properties. The scope includes theoretical and empirical considerations, as well as implications for synthetic biology.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • Some participants inquire about a potential correlation between protein melt temperature and half-life, suggesting that there may be a theoretical or empirical basis for this relationship.
  • Others argue that protein degradation is often regulated through biological processes, such as the ubiquitin-proteasome pathway, which may not directly relate to thermodynamic stability.
  • A participant from a synthetic biology background specifies that they are interested in cases where degradation is not mediated by ubiquitin tags, suggesting that thermal instability may play a role in these instances.
  • One participant expresses a need for references or insights that could clarify the assumption that thermal instability leads to degradation in untagged proteins.
  • Another participant mentions that experienced colleagues believe that untagged proteins degrade due to thermal instability, implying a possible link between melt temperature and half-life.

Areas of Agreement / Disagreement

Participants do not reach a consensus on the relationship between melt temperature and half-life, with multiple competing views regarding the factors influencing protein degradation.

Contextual Notes

The discussion highlights the complexity of protein degradation mechanisms and the potential influence of thermal stability, but lacks definitive references or established models connecting melt temperature to half-life.

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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