Exploring the interplay of stability and function in protein evolution: New methods further elucidate why protein stability is necessarily so tenuous and stability-increasing mutations compromise biological function

Gustavo Caetano-Anollés, Jay Mittenthal

Research output: Contribution to journalReview article

Abstract

A new split β-lactamase assay promises experimental testing of the interplay of protein stability and function. Proteins are sufficiently stable to act effectively within cells. However, mutations generally destabilize structure, with effects on free energy that are comparable to the free energy of folding. Assays of protein functionality and stability in vivo enable a quick study of factors that influence these properties in response to targeted mutations. These assays can help molecular engineering but can also be used to target important questions, including why most proteins are marginally stable, how mutations alter structural makeup, and how thermodynamics, function, and environment shape molecular change. Processes of self-organization and natural selection are determinants of stability and function. Non-equilibrium thermodynamics provides crucial concepts, e.g., cells as emergent energy-dissipating entities that do work and build their own parts, and a framework to study the sculpting role of evolution at different scales.

Original languageEnglish (US)
Pages (from-to)655-658
Number of pages4
JournalBioEssays
Volume32
Issue number8
DOIs
StatePublished - Aug 1 2010

Keywords

  • Fitness
  • Mutation
  • Protein folding
  • Split β-lactamase assay
  • Stability-function tradeoff

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Exploring the interplay of stability and function in protein evolution: New methods further elucidate why protein stability is necessarily so tenuous and stability-increasing mutations compromise biological function'. Together they form a unique fingerprint.

  • Cite this