Themed collection Intrinsically Disordered Proteins

M. Madan Babu introduces this Molecular BioSystems themed issue on intrinsically disordered proteins.

Here, we challenge the conventional structure-centric view of missense mutations. We suggest that disease-associated mutations located in the intrinsically disordered protein regions are more prevalent and have a larger functional impact than previously thought.

This opinion proposes that nature exploited the dynamics of macromolecules to promote and optimize long-distance signaling; signaling is helped by pre-encoded loops and linkers and intrinsic disorder.

We review the literature regarding genome-wide studies of disorder and examine how these studies give rise to new characterizations and categories of this elusive phenomenon.

14-3-3 proteins are ordered hubs that interact with multiple and diverse intrinsically disordered phosphorylated targets opening the possibility to be a master regulator of several signaling networks.

SAXS is a well-established method to characterize disordered biomolecules. Novel ensemble approaches provide quantitative information about the distribution of low-resolution structural parameters, these going beyond traditional single-value descriptors.

The first review discussing Gab proteins from the perspective of structural disorder with implications for their autoregulation and therapeutic strategies.

Fuzziness puts forward a novel model for protein allostery.

The disordered tail ,which may be viewed as DNA recognizing subdomain, may support sliding dynamics and facilitate jumping via a "monkey bar" mechanism in which the flexible tail enhances the brachiation dynamics between two distant DNA fragments.

Conformational distributions of amino acid residues in unfolded peptides differ in their sampling of PPII, β-strand, helix and turn conformations.

This review article focuses on disorder in proteins that bind DNA and RNA and on how this disorder promotes function.

We present recent progress to develop a molecular representation of the disordered state, combining complementary data sets to extract a meaningful description of the conformational behaviour of intrinsically disordered proteins.

In this review we present an overview of protein disorder prediction methods including an analysis of their advantages and shortcomings and an evaluation of their performance on the CASP9 dataset.

Phosphorylation-induced conformational changes in an intrinsically disordered region of ULK1 may provide a mechanism for its action in the regulation of autophagy.

In this review we focus on the conformational and functional impact of fusions between fluorescent proteins and intrinsically disordered domains of various lengths.

In this review the role of intrinsic disorder in AR function is discussed along with the potential to develop new drugs that will target the structurally plastic NTD.

In this review we focus on the experimental data showing the abundance of structural disorder within the nucleoprotein and phosphoprotein from three paramyxoviruses, namely Nipah, Hendra and measles viruses.

The reprogramming transcription factors essential for the induced pluripotent stem cells formation are shown to be highly enriched in intrinsic disorder.

We report the mechanism by which an intrinsic disordered protein, p27^kip1, dynamically optimizes signal transduction through a synergy between intrinsic disorder and functional collective motions.

We examine the percentage of predicted disorder residues within binary and complex interacting proteins (physical and functional interactions respectively) to investigate how the disorder of a protein relates to that of its interacting partners.

Correlation of meta-structure parameters for globular proteins, IDPs and sequence randomized IDPs is different, highlighting a trend in IDP sequences.

These studies revealed the structural state of four putative MoREs within Henipavirus N_TAIL, as well as their role in protein compaction and binding to P_XD.

We show that structural disorder of human proteins coded on the sex chromosomes is significantly higher than the autosome-coded one.

The uncertainty in the reference models and in data is reduced by using appropriate meta predictors of protein disorder. The conservation of disorder is less stable than conservation of structure.

Centrosomal proteins are more disordered and coiled-coil than control proteins of the same organism, and more so in more complex organisms. Disordered regions increase in evolution through large indels, at a rate that is faster in centrosomal than in control proteins, and they evolved faster in phylogenetic branches that experimented a significant growth of cells number.

The 20S proteasome susceptible intrinsically disordered proteins (IDPs) are highly soluble following heat treatment.

Coiled coils have been often linked with intrinsic disorder. Current work focusses on preferences of ordered and disordered coiled coils in various cellular components, molecular functions and biological process.

We identify the role of disordered proteins within the framework of pathway relationships. Three categories of relations are significantly enriched in disordered proteins: gene expression, protein binding and protein phosphorylation.

Occurrence of 20 homorepeats of 6 residues long in 123 proteomes.

Kinetic measurements of the influx of dithionite anions into large unilamellar vesicles show that an impaired membrane integrity caused by α-synuclein oligomers cannot be explained by a simple pore formation process.

Destabilizing osmolytes cause depletion of the most compact structures for intrinsically disordered proteins.

We show that although velocity measurements do yield information on gross conformation, the information is restricted to only the weight averaged sedimentation and diffusion coefficients of the conformational ensemble.

BpUreG, a naturally occurring intrinsically disordered enzyme, undergoes transitions between three major types of conformational ensembles with different degrees of residual structure, depending on temperature and denaturant concentration.

In this work, we tested if there is any biological risk associated with protein disorder at the level of single nucleotide mutations.

The curated instances of the Eukaryotic Linear Motif (ELM) database are analysed to provide a comprehensive overview of the defining attributes of short, linear motifs (SLiMs).

The broad family of LEA proteins are intrinsically disordered proteins (IDPs) with several potential roles in desiccation tolerance, or anhydrobiosis, one of which is to limit desiccation-induced aggregation of cellular proteins.

An analog to Longuet-Higgins' non-rigid molecular group theory arguments can be applied to the structure and reaction dynamics of intrinsically disordered proteins via a somewhat counterintuitive Morse Function treatment inspired by statistical mechanics, providing possible symmetry classifications of the molecular ‘fuzzy lock-and-key’.

Coarse-grained models predict the Hif1α–CBP binding rate, and suggest an induced fit binding mechanism, influenced by non-native interactions.

Comprehensive analysis of the human interactome predicts thousands of conserved, disordered protein motifs of potential functional importance.

Generally mitochondrial proteins have an N-terminal gradient of positive charges and the disordered regions of DNA-binding proteins are negatively charged.

We report the role of π–π interactions in linking binding and function of intrinsically disordered proteins.

Topology-based modeling reveals that NCBD interacts with ACTR via "extended conformational selection" and involves multiple stages of selection and induced folding, which appears highly consistent with H/D-MS and atomistic simulations.