Bioinformatics analysis of correlation between protein function and intrinsic disorder

Vinterhalter, Goran; Kovačević, Jovana; Uversky, Vladimir N.; Pavlović-Lažetić, Gordana

doi:10.1016/j.ijbiomac.2020.11.211

Cited by 8 publications

(11 citation statements)

References 29 publications

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“…Gene ontology (GO) analysis is a common method for annotating genes that can be used to identify gene enrichment in the biological process, cellular component, and molecular function categories. Along with the GO database, the enrichment function of m6A-related genes was analyzed and visualized using the “clusterProfiler” package in R. A significant enrichment with a statistically significant difference was determined based on the following conditions: a false discovery rate < 0.05 and adjusted P < 0.05 ( Pomaznoy et al, 2018 ; Vinterhalter et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Significance of N6-Methyladenosine RNA Methylation Regulators in Immune Infiltrates of Ovarian Cancer

2021

Front. Genet.

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N6-methyladenosine (m6A) RNA methylation regulators play an important role in the occurrence and development of tumors. Here, we aimed to identify the potential roles of m6A RNA methylation regulators in immune infiltrates of ovarian cancer. We obtained two distinct m6A patterns (m6Acluster.A and m6Acluster.B) based on the expression levels of all 21 m6A RNA methylation regulators from The Cancer Genome Atlas (TCGA) database using a consensus clustering algorithm. Differential analysis of m6Acluster.A and m6Acluster.B identified 196 m6A-related genes. We further validated the m6A regulation mechanism based on the 196 m6A-related genes using another consensus clustering algorithm. Considering individual differences, principal component analysis algorithms were used to calculate an m6A score for each sample in order to quantify the m6A patterns. A low m6A score was associated with immune activation and enhanced response to immune checkpoint inhibitors, whereas a high m6A score was associated with tumor progression. Finally, we successfully verified the correlation between m6A regulators and immune microenvironment in OC using our microarray analysis data. In summary, m6A regulators play non-negligible roles in immune infiltrates of ovarian cancer. Our investigation of m6A patterns may help to guide future immunotherapy strategies for advanced ovarian cancer.

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Section: Methodsmentioning

confidence: 99%

Significance of N6-Methyladenosine RNA Methylation Regulators in Immune Infiltrates of Ovarian Cancer

2021

Front. Genet.

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“…For example, IDRs can contain small motifs that steer them into various pathways [79] . IDRs also tend to have very high association rates, potentially through a fly casting mechanism [80,81] afforded by their increased capture radius, which is conducive to rapid responses in signalling networks‐ a functional role in which IDRs are heavily overrepresented [14,24] . The dynamic ensembles of structures that IDRs adopt affords most residues of the chain access to the solvent and thus also binding partners, allowing for a very large number of sequence contexts for binding and rendering the chain accessible for PTMs [14,82] .…”

Section: Protein‐protein Interactions Through Tf Idrsmentioning

confidence: 99%

“…The EDs are well documented to be enriched in structural disorder, where the majority of TFs have been predicted to contain extended disordered regions (Figure 2A,C). [17,24,25] Why are TF EDs so enriched in disorder, that is, what is the functional advantage to the TF in regulating transcription? The answer may lie in the unique physical and chemical features of such regions; i) IDRs assume a dynamic range of conformation, allowing for promiscuous interactions with several partners, enabling TFs to act as hubs to initiate transcription, ii) IDRs are frequently the sites of post-translational modifications (PTMs) which allows sensitive tuning of conformational ensembles and consequently functional output, iii) IDR-DBD interactions can enhance specificity and modulate protein-protein interactions (PPIs), iv) IDR dynamics allow multivalent interactions that can drive phase separation, and many more.…”

Section: Tf Architecturementioning

confidence: 99%

Multifunctional Intrinsically Disordered Regions in Transcription Factors

Már

Nitsenko

Heidarsson

2023

Chemistry A European J

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Eukaryotic transcription factors (TFs) are the final integrators of a complex molecular feedback mechanism that interfaces with the genome, consolidating information for transcriptional regulation. TFs consist of both structured DNAbinding domains and long intrinsically disordered regions (IDRs) embedded with motifs linked to transcriptional control. It is now well established that the dynamic multifunctionality of IDRs is the basis for a wide spectrum of TF functions necessary to navigate and regulate the human genome. This review dissects the chemical features of TF IDRs that endow them with structural plasticity that is central to their functions in the nucleus. Sequence analysis of a set of over 1600 human TFs through AlphaFold was used to identify key features of their IDRs. Recent studies were then highlighted to illustrate IDR involvement in processes such as protein interactions, DNA binding and specificity, chromatin opening, and phase separation. To expand our understanding of TF functions, future directions are suggested for integrating experiments and simulations, from in vitro to living systems.

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“…PONDR was used to investigate intrinsically disordered regions (IDRs) of SARS-CoV-2 Nsp1, which is based on several different predictors such as VL3 and VSL2 [34,35] . In each of these predictors, the first letter refers to the method of characterization (V: Various) and the second letter refers to the length of the disordered region [S: Short (8 -9 residues), and L: Long (40 or more residues)].…”

Section: Nsp1 Intrinsically Disordered Regions (Idrs)mentioning

confidence: 99%

In silico tracking of SARS-CoV-2 Nsp1 structural variants in helix-turn-helix motif

Rezaei¹,

Pereira

Sefidbakht

2021

Preprint

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SARS-CoV-2 non-structural protein 1 (Nsp1) is a virulence factor that inhibits the innate immune response and translation of host mRNAs. Despite the relevance of Nsp1, few studies have been conducted to understand the effect of mutations on Nsp1 structure and function. Here, we provide a molecular dynamics simulation of SARS-CoV-2 and SARS-CoV-1 Nsp1 conformational changes. Our data supports the idea that SARS-CoV-2 Nsp1 has a less compact structure than SARS-CoV-1 Nsp1. Moreover, several mutations in the helix-loop-helix motif of Nsp1 C-terminal that may affect the interactions of the Nsp1-ribosome complex were investigated. Disordered regions in Nsp1 probably affect host-virus interactions, cross-species transmission, and virus-host range. Overall, these findings reinforce the importance of studying Nsp1 conformational changes in new variants and its effect on virulence of SARS-CoV-2, by altering inhibition potency of host mRNA translation efficiency.

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Bioinformatics analysis of correlation between protein function and intrinsic disorder

Cited by 8 publications

References 29 publications

Significance of N6-Methyladenosine RNA Methylation Regulators in Immune Infiltrates of Ovarian Cancer

Significance of N6-Methyladenosine RNA Methylation Regulators in Immune Infiltrates of Ovarian Cancer

Multifunctional Intrinsically Disordered Regions in Transcription Factors

In silico tracking of SARS-CoV-2 Nsp1 structural variants in helix-turn-helix motif

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