Intrinsically unordered proteins: Structural properties, prediction and relevance

Susan Costantini, Marco Miele, Giovanni Colonna

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The interest in intrinsically unordered proteins (IUPs) has greatly increased, as it has become clear that they are very widespread, especially in eukaryotic organisms. The presence of unordered regions in functional proteins is implicated in important biological roles, such as translation and transcriptional regulation, cell signaling and molecular recognition. A number of studies report that for mammals about 75% of their signalling proteins are predicted to contain long unordered regions (30 residues), about half of their total proteins are predicted to contain such long unordered regions, and about 25% of their proteins are predicted to be fully unordered. Other studies report examples of unordered proteins implicated in important cellular processes, undergoing transitions to more structured states upon binding to their target ligands, DNA, or other proteins. The accumulation of such evidence led to the suggestion that the classical protein structurefunction paradigm needs to be reassessed. In fact, the assumption that a folded threedimensional structure is necessary for function has been modified. Although the functions of many proteins are directly related to their three-dimensional structures, numerous proteins that lack intrinsic globular structure under physiological conditions are now recognized. As the amino acid sequence contains the information for protein folding, it was reasoned that, also for proteins that do not fold into three-dimensional structures, the residue sequence should specify protein "nonfolding". Therefore, to test this hypothesis, a large number of methods were developed to predict regions of protein sequences that fail to fold. Their prediction accuracy has been better than expected and this suggests that the information for failure to fold into a regular structure is likely to be inherent within the residue sequence. Because there is an enormous interest in predicting unordered regions of proteins, the analysis of the possibility of predicting protein "unordered" regions was addressed also in the last four editions of CASP experiment. The main aim of this chapter is to present the state of the art of prediction methods of protein unordered regions developed in the last years and their application to specific protein families. In particular, we will focus our discussion on human Sirt-1 and cytokine membrane receptors because our data suggest that these proteins, involved in chronic inflammatory diseases, have unordered structural segments very important for their function.

Original languageEnglish
Title of host publicationProtein Folding
PublisherNova Science Publishers, Inc.
Pages187-216
Number of pages30
ISBN (Print)9781617289903
Publication statusPublished - Jan 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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