Abstract:Currently available computational tools, which are many, provide a researcher with the multitude of options for prediction of intrinsic disorder in a protein of interest and for finding at least some of its disorder-based functions. This chapter provides a highly subjective guideline on how not to be lost in the "dark forest" of available tools for the analysis of intrinsic disorder. By no means it gives a unique pathway through this forest, but simply presents some of the tools the author uses in his everyday… Show more
“…Per‐residue disorder content was evaluated by PONDR predictors, including PONDR‐FIT (Xue et al , 2010 ) and PONDR‐VSL2 (Peng et al , 2005 ). The intrinsic disorder propensities of TSN were evaluated according to the previously described method (Santamaria et al , 2017 ; Uversky, 2017 ). Disorder evaluations together with disorder‐related functional information were retrieved from the D 2 P 2 database ( http://d2p2.pro/ ) (Oates et al , 2013 ).…”
Tudor staphylococcal nuclease (TSN; also known as Tudor‐SN, p100, or SND1) is a multifunctional, evolutionarily conserved regulator of gene expression, exhibiting cytoprotective activity in animals and plants and oncogenic activity in mammals. During stress, TSN stably associates with stress granules (SGs), in a poorly understood process. Here, we show that in the model plant Arabidopsis thaliana, TSN is an intrinsically disordered protein (IDP) acting as a scaffold for a large pool of other IDPs, enriched for conserved stress granule components as well as novel or plant‐specific SG‐localized proteins. While approximately 30% of TSN interactors are recruited to stress granules de novo upon stress perception, 70% form a protein–protein interaction network present before the onset of stress. Finally, we demonstrate that TSN and stress granule formation promote heat‐induced activation of the evolutionarily conserved energy‐sensing SNF1‐related protein kinase 1 (SnRK1), the plant orthologue of mammalian AMP‐activated protein kinase (AMPK). Our results establish TSN as a docking platform for stress granule proteins, with an important role in stress signalling.
“…Per‐residue disorder content was evaluated by PONDR predictors, including PONDR‐FIT (Xue et al , 2010 ) and PONDR‐VSL2 (Peng et al , 2005 ). The intrinsic disorder propensities of TSN were evaluated according to the previously described method (Santamaria et al , 2017 ; Uversky, 2017 ). Disorder evaluations together with disorder‐related functional information were retrieved from the D 2 P 2 database ( http://d2p2.pro/ ) (Oates et al , 2013 ).…”
Tudor staphylococcal nuclease (TSN; also known as Tudor‐SN, p100, or SND1) is a multifunctional, evolutionarily conserved regulator of gene expression, exhibiting cytoprotective activity in animals and plants and oncogenic activity in mammals. During stress, TSN stably associates with stress granules (SGs), in a poorly understood process. Here, we show that in the model plant Arabidopsis thaliana, TSN is an intrinsically disordered protein (IDP) acting as a scaffold for a large pool of other IDPs, enriched for conserved stress granule components as well as novel or plant‐specific SG‐localized proteins. While approximately 30% of TSN interactors are recruited to stress granules de novo upon stress perception, 70% form a protein–protein interaction network present before the onset of stress. Finally, we demonstrate that TSN and stress granule formation promote heat‐induced activation of the evolutionarily conserved energy‐sensing SNF1‐related protein kinase 1 (SnRK1), the plant orthologue of mammalian AMP‐activated protein kinase (AMPK). Our results establish TSN as a docking platform for stress granule proteins, with an important role in stress signalling.
“…According to the method described by Uversky et al (2017) [ 102 , 103 ], the intrinsic disorder propensities of target proteins were evaluated using four algorithms from the PONDR family (PONDR-FIT, PONDR ® VSL2, PONDR ® VL3 and PONDR ® VLXT) [ 36 , 37 , 38 , 39 , 40 ], as well as IUPred-long and IUPred-short [ 41 ]. The mean intrinsic disorder value of each protein was calculated by averaging the disorder profiles of the above six predictors.…”
DNA methylation is an important epigenetic modification that needs to be carefully controlled as a prerequisite for normal early embryogenesis. Compelling evidence now suggests that four maternal-effect proteins, primordial germ cell 7 (PGC7), zinc finger protein 57 (ZFP57), tripartite motif-containing 28 (TRIM28) and DNA methyltransferase (cytosine-5) 1 (DNMT1) are involved in the maintenance of DNA methylation. However, it is still not fully understood how these maternal-effect proteins maintain the DNA methylation imprint. We noticed that a feature common to these proteins is the presence of significant levels of intrinsic disorder so in this study we started from an intrinsic disorder perspective to try to understand these maternal-effect proteins. To do this, we firstly analysed the intrinsic disorder predispositions of PGC7, ZFP57, TRIM28 and DNMT1 by using a set of currently available computational tools and secondly conducted an intensive literature search to collect information on their interacting partners and structural characterization. Finally, we discuss the potential effect of intrinsic disorder on the function of these proteins in maintaining DNA methylation.
“…On the other hand, proteins with IDRs (intrinsically disordered regions) cannot form stable secondary structures and many IDRs contain a small biased amino acid composition which is referred to as low complexity domains (LCDs) (Das et al, 2014;. IDRs have been shown to be prone to aggregation upon stress conditions (Uversky, 2017).…”
Cellular stress not only activates many signaling pathways, but also lead to the remodeling of the cytoplasm through the formation of biocondensates/stress assemblies.
Membraneless organellesThere are numerous compartments or organelles in eukaryotic cells and eukaryotic cells are compartmentalized by membrane-bound compartments to ensure the biochemical reactions and cellular functions(
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