The robustness and innovability of protein folds

Curr Opin Struct Biol. 2014 Jun;26:131-8. doi: 10.1016/j.sbi.2014.06.007. Epub 2014 Jul 17.

Abstract

Assignment of protein folds to functions indicates that >60% of folds carry out one or two enzymatic functions, while few folds, for example, the TIM-barrel and Rossmann folds, exhibit hundreds. Are there structural features that make a fold amenable to functional innovation (innovability)? Do these features relate to robustness--the ability to readily accumulate sequence changes? We discuss several hypotheses regarding the relationship between the architecture of a protein and its evolutionary potential. We describe how, in a seemingly paradoxical manner, opposite properties, such as high stability and rigidity versus conformational plasticity and structural order versus disorder, promote robustness and/or innovability. We hypothesize that polarity--differentiation and low connectivity between a protein's scaffold and its active-site--is a key prerequisite for innovability.

Publication types

  • Review

MeSH terms

  • Catalytic Domain
  • Evolution, Molecular
  • Proteins / chemistry*
  • Proteins / metabolism

Substances

  • Proteins