Kinetic traps and life

“It is well known that the thermodynamically stable state of proteins in a crowded environment is insoluble fibrils” [ Proc. Natl. Acad. Sci. vol. 119 pp. e2122078119 ’22 ].  However even under ideal conditions the time scale for their formation is hours to days [ Nat. Rev. Mol. Cell Biol. 15, 384–396 (2014) ].  Hopefully it’s even longer (decades) for senile plaques (abeta) neurofibrils (tau) and Lewy bodies (alpha-synuclein) to form.  The fact that equilibrium takes such a long time to reach, allows rapid synthesis and degradation of proteins to avoid their aggregation.  So we live because our proteins are trapped in a less the equilibrium (metastable) state by kinetics — e.g. a kinetic trap.

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  • Peter Shenkin  On January 28, 2022 at 7:38 am

    As far as I know, Cy Levinthal was the first to have suggested that the native forms of proteins might be due to kinetics and might not be the most stable configuration. See the Wikipedia article on the “Levinthal Paradox”:

    • luysii  On January 28, 2022 at 11:53 am

      Levinthal really was way ahead of curve, wasn’t he? Little did he know that waiting outside the ribosome exit tunnel were chaperones, limiting the conformation space the newly formed peptide could explore

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