Intrinsic Disorder in Tetratricopeptide Repeat Proteins

Bibber, Nathan W. Van; Haerle, Cornelia; Khalife, Roy; Xue, Bin; Uversky, Vladimir N.

doi:10.3390/ijms21103709

Cited by 14 publications

(4 citation statements)

References 149 publications

(243 reference statements)

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“…This PPI network with an average node degree of 13.8, average local clustering coefficient of 0.871, expected number of edges of 49, and PPI enrichment p -value of <10 –16 includes 34 proteins/genes connected by 235 interactions. The presence of high levels of functional disorder in human RGPD4 is in line with the results of our global analysis of a set of human TPR proteins, where it was shown that these TPR proteins contain different levels of intrinsic disorder and possess functional IDPRs that are utilized in the PPIs and often serve as targets of various PTMs.…”

Section: Resultssupporting

confidence: 86%

Intrinsic Disorder in Human Proteins Encoded by Core Duplicon Gene Families

et al. 2020

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Segmental duplications (i.e., highly homologous DNA fragments greater than 1 kb in length that are present within a genome at more than one site) are typically found in genome regions that are prone to rearrangements. A noticeable fraction of the human genome (∼5%) includes segmental duplications (or duplicons) that are assumed to play a number of vital roles in human evolution, human-specific adaptation, and genomic instability. Despite their importance for crucial events such as synaptogenesis, neuronal migration, and neocortical expansion, these segmental duplications continue to be rather poorly characterized. Of particular interest are the core duplicon gene (CDG) families, which are replicates sharing common “core” DNA among the randomly attached pieces and which expand along single chromosomes and might harbor newly acquired protein domains. Another important feature of proteins encoded by CDG families is their multifunctionality. Although it seems that these proteins might possess many characteristic features of intrinsically disordered proteins, to the best of our knowledge, a systematic investigation of the intrinsic disorder predisposition of the proteins encoded by core duplicon gene families has not been conducted yet. To fill this gap and to determine the degree to which these proteins might be affected by intrinsic disorder, we analyzed a set of human proteins encoded by the members of 10 core duplicon gene families, such as NBPF, RGPD, GUSBP, PMS2P, SPATA31, TRIM51, GOLGA8, NPIP, TBC1D3, and LRRC37. Our analysis revealed that the vast majority of these proteins are highly disordered, with their disordered regions often being utilized as means for the protein–protein interactions and/or targeted for numerous posttranslational modifications of different nature.

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Section: Resultssupporting

confidence: 86%

Intrinsic Disorder in Human Proteins Encoded by Core Duplicon Gene Families

et al. 2020

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“…However, with a few exceptions, 32,33 these servers are not designed with genome‐scale structural bioinformatics or comparative genomics/proteomics in mind. We previously developed a web‐crawler style disorder predictor for internal usage that was implemented into a tool we refer to as Disorder Spider (DiSpi) in our previous studies, see for example, refs 34–39 . DiSpi works by first aggregating disorder profiles from six well‐known disorder predictors: PONDR VLXT, 40 PONDR VL3, 41 PONDR VLS2B, 42 PONDR‐FIT, 43 IUPred‐Short, and IUPred‐Long 44 .…”

Section: Introductionmentioning

confidence: 99%

“…We previously developed a web-crawler style disorder predictor for internal usage that was implemented into a tool we refer to as Disorder Spider (DiSpi) in our previous studies, see for example, refs. [34][35][36][37][38][39] DiSpi works by first aggregating disorder profiles from six well-known disorder predictors: PONDR VLXT, 40 PONDR VL3, 41 PONDR VLS2B, 42 PONDR-FIT, 43 IUPred-Short, and IUPred-Long. 44 Then, a mean disorder profile (MDP) is computed along with the standard error.…”

Section: Introductionmentioning

confidence: 99%

Rapid prediction and analysis of protein intrinsic disorder

Dayhoff

Uversky

2022

Protein Science

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Protein intrinsic disorder is found in all kingdoms of life and is known to underpin numerous physiological and pathological processes. Computational methods play an important role in characterizing and identifying intrinsically disordered proteins and protein regions. Herein, we present a new high‐efficiency web‐based disorder predictor named Rapid Intrinsic Disorder Analysis Online (RIDAO) that is designed to facilitate the application of protein intrinsic disorder analysis in genome‐scale structural bioinformatics and comparative genomics/proteomics. RIDAO integrates six established disorder predictors into a single, unified platform that reproduces the results of individual predictors with near‐perfect fidelity. To demonstrate the potential applications, we construct a test set containing more than one million sequences from one hundred organisms comprising over 420 million residues. Using this test set, we compare the efficiency and accessibility (i.e., ease of use) of RIDAO to five well‐known and popular disorder predictors, namely: AUCpreD, IUPred3, metapredict V2, flDPnn, and SPOT‐Disorder2. We show that RIDAO yields per‐residue predictions at a rate two to six orders of magnitude greater than the other predictors and completely processes the test set in under an hour. RIDAO can be accessed free of charge at https://ridao.app.

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“…The predicted percent of intrinsically disordered residues (PPIDR) is defined as the number of disordered residues divided by the length of the sequence. Based on their levels of intrinsic disorder, proteins are classified as highly disordered (MDS ≥ 0.5, PPIDR ≥ 30%), moderately disordered (0.25 ≤ MDS < 0.5, 10% ≤ PPIDR < 30%) and ordered (MDS < 0.25, PPIDR < 10%) [93]. The MDS is not directly related to PPIDR (in particular, at 100% PPIDR value of MDS can be anything in the range from 0.5 to 1); therefore, these two methods of protein intrinsic disorder evaluation should be analyzed using correlation.…”

Section: Disorder Prediction: Description and Comparison Of Algorithmsmentioning

confidence: 99%

Chaotic aging: Intrinsically disordered proteins in aging-related processes

Manyilov

Ilyinsky

Nesterov

et al. 2023

Preprint

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The development of aging is associated with the disruption of key cellular processes manifested as well-established hallmarks of aging. Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) have no stable tertiary structure that provide them a power to be configurable hubs in signaling cascades and regulate many processes, potentially including those related to aging. There is a need to clarify the roles of IDPs/IDRs in aging. The dataset of 1624 aging-related proteins was collected from established aging databases and experimental studies. There is a noticeable presence of IDPs/IDRs, accounting for about 36% of the aging-related dataset, which is comparable to the disorder content of the whole human proteome (about 40%). A Gene Ontology analysis of the our Aging proteome reveals an abundance of IDPs/IDRs in one-third of aging-associated processes, especially in genome regulation. Signaling pathways associated with aging also contain IDPs/IDRs on different hierarchical levels. Protein-protein interaction network analysis showed that IDPs present in different clusters associated with different aging hallmarks. Protein cluster with IDPs enrichment and high liquid-liquid phase separation (LLPS) probability has 'nuclear' localization and DNA-associated functions, related to aging hallmarks: genomic instability, telomere attrition, epigenetic alterations, stem cells exhaustion. Some IDPs related to aging with high LLPS propensity were identified as 'dangerous' based on the prediction of their propensity to aggregation. Overall, our analyses indicate that IDPs/IDRs play significant roles in aging-associated processes, particularly in the regulation of DNA functioning. IDP aggregation, which can lead to loss-of-function and toxicity, could be critically harmful to the cell. A structure-based analysis of aging and the identification of proteins that are particularly susceptible to disturbances can enhance our understanding of the molecular mechanisms of aging and open up new avenues for slowing it down.

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Intrinsic Disorder in Tetratricopeptide Repeat Proteins

Cited by 14 publications

References 149 publications

Intrinsic Disorder in Human Proteins Encoded by Core Duplicon Gene Families

Intrinsic Disorder in Human Proteins Encoded by Core Duplicon Gene Families

Rapid prediction and analysis of protein intrinsic disorder

Chaotic aging: Intrinsically disordered proteins in aging-related processes

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