Intrinsically Disordered Proteins: Critical Components of the Wetware

Chem Rev. 2022 Mar 23;122(6):6614-6633. doi: 10.1021/acs.chemrev.1c00848. Epub 2022 Feb 16.

Abstract

Despite the wealth of knowledge gained about intrinsically disordered proteins (IDPs) since their discovery, there are several aspects that remain unexplored and, hence, poorly understood. A living cell is a complex adaptive system that can be described as a wetware─a metaphor used to describe the cell as a computer comprising both hardware and software and attuned to logic gates─capable of "making" decisions. In this focused Review, we discuss how IDPs, as critical components of the wetware, influence cell-fate decisions by wiring protein interaction networks to keep them minimally frustrated. Because IDPs lie between order and chaos, we explore the possibility that they can be modeled as attractors. Further, we discuss how the conformational dynamics of IDPs manifests itself as conformational noise, which can potentially amplify transcriptional noise to stochastically switch cellular phenotypes. Finally, we explore the potential role of IDPs in prebiotic evolution, in forming proteinaceous membrane-less organelles, in the origin of multicellularity, and in protein conformation-based transgenerational inheritance of acquired characteristics. Together, these ideas provide a new conceptual framework to discern how IDPs may perform critical biological functions despite their lack of structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Intrinsically Disordered Proteins* / chemistry
  • Organelles / chemistry
  • Protein Conformation
  • Protein Interaction Maps

Substances

  • Intrinsically Disordered Proteins