Recent advances suggest increased influence of selective pressure in allostery
| Autor: | Nick V. Grishin, Archana S. Bhat, Richard Dustin Schaeffer, Lisa N. Kinch, Kirill E. Medvedev |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular 0303 health sciences Somatic cell Allosteric regulation Druggability Proteins Computational biology Biology Article 03 medical and health sciences Negative selection 0302 clinical medicine Allosteric Regulation Structural Biology Catalytic Domain Animals Humans Molecular Biology Allosteric Site 030217 neurology & neurosurgery Protein Binding 030304 developmental biology |
| Zdroj: | Curr Opin Struct Biol |
| ISSN: | 0959-440X |
| DOI: | 10.1016/j.sbi.2020.02.004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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