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, i.e. the sequence of a protein determines its structure, and structure determines function. However, a class of polypeptide segments called Intrinsically Disordered Regions (IDRs) defies this postulate. In this presentation, I will first describe established and emerging ideas about how disordered regions contribute to protein function. I will then discuss molecular principles of how regulatory mechanisms such as alternative splicing and asymmetric mRNA localization of transcripts encoding disordered segments 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.