The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease

Biochem Soc Trans. 2016 Oct 15;44(5):1185-1200. doi: 10.1042/BST20160172.

Abstract

In the 1960s, Christian Anfinsen postulated that the unique three-dimensional structure of a protein is determined by its amino acid sequence. This work laid the foundation for the sequence-structure-function paradigm, which states that the sequence of a protein determines its structure, and structure determines function. However, a class of polypeptide segments called intrinsically disordered regions does not conform to this postulate. In this review, I will first describe established and emerging ideas about how disordered regions contribute to protein function. I will then discuss molecular principles by which regulatory mechanisms, such as alternative splicing and asymmetric localization of transcripts that encode disordered regions, can increase the functional versatility of proteins. Finally, I will discuss how disordered regions contribute to human disease and the emergence of cellular complexity during organismal evolution.

Keywords: RNA localization; alternative splicing; biological networks; gene expression and regulation; intrinsically disordered proteins; protein turnover.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Apoptosis / genetics
  • Disease / genetics*
  • Humans
  • Intrinsically Disordered Proteins / chemistry
  • Intrinsically Disordered Proteins / genetics*
  • Intrinsically Disordered Proteins / metabolism*
  • Models, Molecular
  • Protein Conformation
  • Protein Folding
  • Structure-Activity Relationship

Substances

  • Intrinsically Disordered Proteins