Intrinsic disorder in DNA-binding proteins

© 2016 Nova Science Publishers, Inc. Intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDPRs) do not have unique 3D structures under physiological conditions. They share specific sequence features such as low overall hydrophobicity and high net charge. They also have a distinctive conformational behavior, with large hydrodynamic volumes, low contents of ordered secondary structure, and high structural heterogeneity. Despite their flexibility, some IDPs/IDPRs may undergo disorder to order transitions in the presence of natural ligands. IDPs carry out numerous biological functions, including those associated with signaling, transcription regulation, DNA condensation, cell division, and cellular differentiation. Bioinformatic prediction tools revealed that as many as 50% of eukaryotic proteins are likely to contain functionally important long disordered regions. The highest number of predicted IDPs or IDPRs corresponds to DNA-binding proteins. However, the number of experimentally confirmed IDP/IDPRs included in the Disprot database is quite smaller, comprising only 73 proteins. This functional subclass is composed mainly of transcription factors, DNA metabolism proteins and chromosomal architectural proteins like histones and high mobility group proteins (HMGs). In this chapter we will focus on the DNA-binding IDPs and how intrinsic disorder affects their function.