title: The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease.
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.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, U.K.
authors.forename: M Madan
authors.initials: MM
authors.lastname: Babu
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics; D004194:Disease / Q000235:genetics*; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D013329:Structure-Activity Relationship
chemical_list: D064267:Intrinsically Disordered Proteins
keywords: RNA localization; alternative splicing; biological networks; gene expression and regulation; intrinsically disordered proteins; protein turnover