Abundance of intrinsic disorder in SV-IV, a multifunctional androgen-dependent protein secreted from rat seminal vesicle

The potent immunomodulatory, anti-inflammatory and procoagulant properties of the
protein no. 4 secreted from the rat seminal vesicle epithelium (SV-IV) have been
previously found to be modulated by a supramolecular monomer-trimer equilibrium.
More structural details that integrate experimental data into a predictive framework
have recently been reported. Unfortunately, homology modelling and fold-recognition
strategies were not successful in creating a theoretical model of the structural
organization of SV-IV. It was inferred that the global structure of SV-IV is not similar
to any protein of known three-dimensional structure. Reversing the classical approach
to the sequence-structure-function paradigm, in this paper we report on novel
information obtained by comparing physicochemical parameters of SV-IV with two
datasets made of intrinsically unfolded and ideally globular proteins. In addition, we
have analysed the SV-IV sequence by several publicly available disorder-oriented
predictors. Overall, disorder predictions and a re-examination of existing experimental
data strongly suggest that SV-IV needs large plasticity to efficiently interact with the
different targets that characterize its multifaceted biological function and should be
therefore better classified as an intrinsically disordered protein

Meta-structure correlation in protein space unveils different selection rules for folded and intrinsically disordered proteins

The number of existing protein sequences spans a very small fraction of sequence space. Natural proteins have overcome a strong negative selective pressure to avoid the formation of insoluble aggregates. Stably folded globular proteins and intrinsically disordered proteins (IDP) use alternative solutions to the aggregation problem. While in globular proteins folding minimizes the access to aggregation prone regions IDPs on average display large exposed contact areas. Here, we introduce the concept of average meta-structure correlation map to analyze sequence space. Using this novel conceptual view we show that representative ensembles of folded and ID proteins show distinct characteristics and responds differently to sequence randomization. By studying the way evolutionary constraints act on IDPs to disable a negative function (aggregation) we might gain insight into the mechanisms by which function - enabling information is encoded in IDPs

DisProt: the Database of Disordered Proteins

The Database of Protein Disorder (DisProt) links structure and function information for intrinsically disordered proteins (IDPs). Intrinsically disordered proteins do not form a fixed three-dimensional structure under physiological conditions, either in their entireties or in segments or regions. We define IDP as a protein that contains at least one experimentally determined disordered region. Although lacking fixed structure, IDPs and regions carry out important biological functions, being typically involved in regulation, signaling and control. Such functions can involve high-specificity low-affinity interactions, the multiple binding of one protein to many partners and the multiple binding of many proteins to one partner. These three features are all enabled and enhanced by protein intrinsic disorder. One of the major hindrances in the study of IDPs has been the lack of organized information. DisProt was developed to enable IDP research by collecting and organizing knowledge regarding the experimental characterization and the functional associations of IDPs. In addition to being a unique source of biological information, DisProt opens doors for a plethora of bioinformatics studies. DisProt is openly available at

Multi-scale sequence correlations increase proteome structural disorder and promiscuity

Numerous experiments demonstrate a high level of promiscuity and structural disorder in organismal proteomes. Here we ask the question what makes a protein promiscuous, i.e., prone to non-specific interactions, and structurally disordered. We predict that multi-scale correlations of amino acid positions within protein sequences statistically enhance the propensity for promiscuous intra- and inter-protein binding. We show that sequence correlations between amino acids of the same type are statistically enhanced in structurally disordered proteins and in hubs of organismal proteomes. We also show that structurally disordered proteins possess a significantly higher degree of sequence order than structurally ordered proteins. We develop an analytical theory for this effect and predict the robustness of our conclusions with respect to the amino acid composition and the form of the microscopic potential between the interacting sequences. Our findings have implications for understanding molecular mechanisms of protein aggregation diseases induced by the extension of sequence repeats

ComSin: database of protein structures in bound (complex) and unbound (single) states in relation to their intrinsic disorder

Most of the proteins in a cell assemble into complexes to carry out their function. In this work, we have created a new database (named ComSin) of protein structures in bound (complex) and unbound (single) states to provide a researcher with exhaustive information on structures of the same or homologous proteins in bound and unbound states. From the complete Protein Data Bank (PDB), we selected 24 910 pairs of protein structures in bound and unbound states, and identified regions of intrinsic disorder. For 2448 pairs, the proteins in bound and unbound states are identical, while 7129 pairs have sequence identity 90% or larger. The developed server enables one to search for proteins in bound and unbound states with several options including sequence similarity between the corresponding proteins in bound and unbound states, and validation of interaction interfaces of protein complexes. Besides that, through our web server, one can obtain necessary information for studying disorder-to-order and order-to-disorder transitions upon complex formation, and analyze structural differences between proteins in bound and unbound states. The database is available at http://antares.protres.ru/comsin/