Recent advances suggest increased influence of selective pressure in allostery

Archana S. Bhat, Richard Dustin Schaeffer, Lisa Kinch, Kirill E. Medvedev, Nick V. Grishin

Research output: Contribution to journalReview article

Abstract

Allosteric regulation of protein functions is ubiquitous in organismal biology, but the principles governing its evolution are not well understood. Here we discuss recent studies supporting the large-scale existence of latent allostery in ancestor proteins of superfamilies. As suggested, the evolution of allostery could be driven by the need for specificity in paralogs of slow evolving protein complexes with conserved active sites. The same slow evolution is displayed by purifying selection exhibited in allosteric proteins with somatic mutations involved in cancer, where disease-associated mutations are enriched in both orthosteric and allosteric sites. Consequently, disease-associated variants can be used to identify druggable allosteric sites that are specific for paralogs in protein superfamilies with otherwise similar functions.

Original languageEnglish (US)
Pages (from-to)183-188
Number of pages6
JournalCurrent Opinion in Structural Biology
Volume62
DOIs
StatePublished - Jun 2020

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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