Prediction of protein disorder based on IUPred

Dosztányi, Zsuzsanna

doi:10.1002/pro.3334

Cited by 178 publications

(151 citation statements)

References 75 publications

(89 reference statements)

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“…A, B. Prediction of protein disorder using the IUPRED server (Dosztanyi, 2018). The ANCHOR score predicts the transition from unstructured to structured depending on a binding partner.…”

Section: Figure 1: Purification and Subunit Arrangement Of The S Cermentioning

confidence: 99%

DNA-dependent macromolecular condensation drives self-assembly of the meiotic DNA break machinery

Wang

et al. 2020

Preprint

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Formation of meiotic DNA double-strand breaks (DSBs) by Spo11is tightly regulated and tied to chromosome structure, but the higher-order assemblies that execute and control DNA breakage are poorly understood. We address this question through molecular characterization of Saccharomyces cerevisiae RMM proteins (Rec114, Mei4 and Mer2)-essential, conserved components of the DSB machinery. Each subcomplex of Rec114-Mei4 (2:1 heterotrimer) or Mer2 (homotetrameric coiled coil) is monodisperse in solution, but they independently condense with DNA into dynamic, reversible nucleoprotein clusters that share properties with phase-separated systems. Multivalent interactions drive condensation, which correlates with DSB formation in vivo. Condensates fuse into mixed Rec114-Mei4-Mer2 clusters that further recruit Spo11 complexes. Our data show how the DSB machinery self-assembles on chromosome axes to create centers of DSB activity. We propose that multilayered control of Spo11 arises from recruitment of regulatory components and modulation of biophysical properties of the condensates.The role of Rec114-Mei4 and Mer2 in meiosis

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“…A, B. Prediction of protein disorder using the IUPRED server (Dosztanyi, 2018). The ANCHOR score predicts the transition from unstructured to structured depending on a binding partner.…”

Section: Figure 1: Purification and Subunit Arrangement Of The S Cermentioning

confidence: 99%

DNA-dependent macromolecular condensation drives self-assembly of the meiotic DNA break machinery

Wang

et al. 2020

Preprint

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“…The amino acid sequence of Them1 from Mus musculus was acquired from UniProt 33 and analyzed with multiple servers. The IUPRED2A server was used to predict intrinsic disorder and ANCHOR binding regions [34][35][36][37] . The Prion-like Amino Acid Composition (PLAAC) server was used to predict prion like regions through the prion like domains (PLD) and FOLD curves 38 .…”

Section: Image Processing and Quantification Of Fluorescence Signal mentioning

confidence: 99%

Thioesterase Superfamily Member 1 Undergoes Stimulus-coupled Reorganization to Regulate Metabolism

Imai

Goyal

et al. 2020

Preprint

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In brown adipose tissue, cold exposure promotes thermogenesis, in large part by increasing mitochondrial -oxidation of lipid droplet-derived fatty acids. This process is suppressed by thioesterase superfamily member 1 (Them1), a long chain fatty acyl-CoA thioesterase that is highly upregulated by cold ambient temperatures. Them1 reduces fatty acid availability for oxidation in mitochondria and limits thermogenesis by cellular mechanisms that are not well defined. We show that Them1 regulates metabolism by undergoing marked intracellular conformational changes that occur in response to -adrenergic stimulation. Mechanistically, Them1 formed puncta that were localized near LD and mitochondria in an immortalized brown adipose cell line. In response to stimulation by norepinephrine, Them1 was phosphorylated by PKC at S15, which specifically inhibited puncta formation and resulted in a diffuse intracellular localization. This change in Them1 localization also occurred after stimulation in vivo. Puncta formation activated Them1 metabolic activity in vitro, as evidenced by suppression of oxygen consumption following -adrenergic stimulation. We show by correlative light and electron microscopy that puncta are biomolecular condensates (also known as membraneless organelles) that typically form by phase separation. Them1 contains one intrinsically disordered region at the N-terminus with multiple interacting motifs that is frequently observed in phaseseparating proteins. Phosphorylation, which is known to disrupt phase separation and aggregation, results in a diffuse Them1 localization. Our data thus establish that Them1 forms intracellular biomolecular condensates that limit fatty acid oxidation and suppress thermogenesis. During a period of energy demand, the condensates are disrupted by phosphorylation to allow for maximal thermogenesis. The stimulus-coupled reorganization of Them1 thus provides fine-tuning of thermogenesis and energy expenditure.

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“…The online tool IUPRED (Dosztanyi, 2018) predicted disorder to be high across the EWS Nterminus, but low in the ALE ( Figure S4A). Phyre2 (Kelley et al, 2015) was used to predict secondary structure.…”

Section: Ntews Promotes Phenotypes Related To Oncogenesismentioning

confidence: 99%

Androgen signaling connects short isoform production to breakpoint formation at Ewing sarcoma breakpoint region 1 via an R-loop-dependent mechanism

Nicholas

Hollenhorst

2020

Preprint

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Ewing's sarcoma is most prevalent in adolescent males and is almost always the result of a chromosomal rearrangement that creases a fusion gene with EWSR1 as the 5' fusion partner.Why EWSR1 is more commonly rearranged than other, similar genes and why Ewing's sarcoma is predisposed to adolescent males is not known. We found that in prostate cancer, androgen signaling upregulated a 5' EWSR1 isoform by promoting usage of an intronic polyadenylation site proximal to the Ewing's sarcoma breakpoint hotspot. An intronic Androgen Receptor (AR) binding site was necessary for this upregulation. Strikingly, androgen signaling drove high levels of breakpoint formation in EWSR1. Androgen signaling also promoted R-loop formation and Rloops were necessary for breakpoint formation. These data suggest that aberrant androgen signaling leads to R-loop-mediated DNA damage at the EWSR1 breakpoint hotspot and subsequent misrepair could promote EWSR1 gene fusions in Ewing's sarcoma.

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Prediction of protein disorder based on IUPred

Cited by 178 publications

References 75 publications

DNA-dependent macromolecular condensation drives self-assembly of the meiotic DNA break machinery

DNA-dependent macromolecular condensation drives self-assembly of the meiotic DNA break machinery

Thioesterase Superfamily Member 1 Undergoes Stimulus-coupled Reorganization to Regulate Metabolism

Androgen signaling connects short isoform production to breakpoint formation at Ewing sarcoma breakpoint region 1 via an R-loop-dependent mechanism

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