Unfoldomes and Unfoldomics: Introducing Intrinsically Disordered Proteins

Abstract

The last decade and a half has witnessed the fall of one of the major paradigms in structural biology. Contrary to the more than a hundred year-old belief that unique protein function is defined by unique crystal-like protein structure which is encoded in unique amino acid sequence, many biologically active proteins lack stable tertiary and/or secondary structure under physiological conditions in vitro. These intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are very different from ordered proteins and domains at the variety of levels, starting from the specific and well-recognizable amino acid composition and sequence biases and ending with engagement in biological functions non-accessible to entities with unique and fixed structures. IDPs/IDPRs are highly abundant in nature, and many of them are associated with various human diseases. The functional repertoire of IDPs complements the functions of ordered proteins, with IDPs being often involved in regulation, signaling, and control. Due to their exceptional commonness within the protein universe, combined with a set of specific structural and conformational features, and broad and unique functional repertoire, IDPs and hybrid proteins possessing ordered domains and functional IDPRs clearly comprise unfoldomes within all known proteomes. This chapter provides a brief description of IDPs/IDPRs and shows the place of these exceptionally interesting creatures within the protein kingdom.