The mysterious unfoldome: structureless, underappreciated, yet vital part of any given proteome.
Contrarily to the general believe, many biologically active proteins lack stable tertiary and/or secondary structure under physiological conditions in vitro. These intrinsically disordered proteins (IDPs) 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. Since IDPs constitute a significant portion of any given proteome, they can be combined in an unfoldome; which is a portion of the proteome including all IDPs (also known as natively unfolded proteins, therefore, unfoldome), and describing their functions, structures, interactions, evolution, and so forth. Amino acid sequence and compositions of IDPs are very different from those of ordered proteins, making possible reliable identification of IDPs at the proteome level by various computational means. Furthermore, IDPs possess a number of unique structural properties and are characterized by a peculiar conformational behavior, including their high stability against low pH and high temperature and their structural indifference toward the unfolding by strong denaturants. These peculiarities were shown to be useful for elaboration of the experimental techniques for the large-scale identification of IDPs in various organisms. Some of the computational and experimental tools for the unfoldome discovery are discussed in this review.
Uversky
Vladimir N
VN
Institute for Intrinsically Disordered Protein Research, The Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. vuversky@iupui.edu
D000596:Amino Acids / Q000737:chemistry; D019295:Computational Biology; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D017510:Protein Folding; D020543:Proteome / Q000737:chemistry* / Q000502:physiology*
D000596:Amino Acids; D020543:Proteome