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Protein stability promotes evolvability.

Jesse D Bloom1, Sy T Labthavikul, Christopher R Otey

  • 1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. jesse.bloom@gmail.com

Proceedings of the National Academy of Sciences of the United States of America
|April 4, 2006
PubMed
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Protein extra stability enhances evolvability by increasing mutational robustness. This allows proteins to accept more beneficial mutations, leading to new functions and improved biochemical tasks, aiding both natural and directed evolution.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Evolutionary Biology

Background:

  • The biophysical basis for protein evolvability remains largely unexplored.
  • Understanding how proteins adapt to diverse biochemical functions is crucial.

Purpose of the Study:

  • To investigate the link between protein stability and evolvability.
  • To determine if increased protein stability enhances a protein's capacity to evolve.

Main Methods:

  • Computational simulations using model lattice proteins.
  • Experimental evolution of cytochrome P450 BM3 variants with varying stability.

Main Results:

  • Simulations showed extra stability increases evolvability by allowing tolerance to more mutations.

Related Experiment Videos

  • Experimentally, stabilized cytochrome P450 BM3 variants exhibited higher rates of new or improved functions.
  • Only stabilized variants could tolerate mutations for novel activities, like drug hydroxylation.

    • Conclusions:

    • Protein extra stability is a key factor enhancing evolvability through mutational robustness.
    • This relationship can be exploited to discover novel protein functions.
    • Natural evolution may also leverage protein stability for adaptation.