Intrinsic protein disorder in histone lysine methylation

Histone lysine methyltransferases (HKMTs), catalyze mono-, di- and trimethylation of lysine residues, resulting in a regulatory pattern that controls gene expression. Their involvement in many different cellular processes and diseases makes HKMTs an intensively studied protein group, but scientific interest so far has been concentrated mostly on their catalytic domains. In this work we set out to analyze the structural heterogeneity of human HKMTs and found that many contain long intrinsically disordered regions (IDRs) that are conserved through vertebrate species. Our predictions show that these IDRs contain several linear motifs and conserved putative binding sites that harbor cancer-related SNPs. Although there are only limited data available in the literature, some of the predicted binding regions overlap with interacting segments identified experimentally. The importance of a disordered binding site is illustrated through the example of the ternary complex between MLL1, menin and LEDGF/p75. Our suggestion is that intrinsic protein disorder plays an as yet unrecognized role in epigenetic regulation, which needs to be further elucidated through structural and functional studies aimed specifically at the disordered regions of HKMTs. Reviewers: This article was reviewed by Arne Elofsson and Piotr Zielenkiewicz. © 2016 The Author(s)

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

Reduction in Structural Disorder and Functional Complexity in the Thermal Adaptation of Prokaryotes

Genomic correlates of evolutionary adaptation to very low or very high optimal growth temperature (OGT) values have been the subject of many studies. Whereas these provided a protein-structural rationale of the activity and stability of globular proteins/enzymes, the point has been neglected that adaptation to extreme temperatures could also have resulted from an increased use of intrinsically disordered proteins (IDPs), which are resistant to these conditions in vitro. Contrary to these expectations, we found a conspicuously low level of structural disorder in bacteria of very high (and very low) OGT values. This paucity of disorder does not reflect phylogenetic relatedness, i.e. it is a result of genuine adaptation to extreme conditions. Because intrinsic disorder correlates with important regulatory functions, we asked how these bacteria could exist without IDPs by studying transcription factors, known to harbor a lot of function-related intrinsic disorder. Hyperthermophiles have much less transcription factors, which have reduced disorder compared to their mesophilic counterparts. On the other hand, we found by systematic categorization of proteins with long disordered regions that there are certain functions, such as translation and ribosome biogenesis that depend on structural disorder even in hyperthermophiles. In all, our observations suggest that adaptation to extreme conditions is achieved by a significant functional simplification, apparent at both the level of the genome and individual genes/proteins

DisProt: intrinsic protein disorder annotation in 2020

The Database of Protein Disorder (DisProt, URL: https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the ‘dark’ proteome

Caractérisation des périodes de sécheresse sur le domaine de l'Afrique simulée par le Modèle Régional Canadien du Climat (MRCC5)

Les conséquences des changements climatiques sur la fréquence ainsi que sur l'intensité des précipitations auront un impact direct sur les périodes de sécheresse et par conséquent sur différents secteurs économiques tels que le secteur de l'agriculture. Ainsi, dans cette étude, l'habilité du Modèle Régional Canadien du Climat (MRCC5) à simuler les différentes caractéristiques des périodes de sécheresse est évaluée pour 4 seuils de précipitation soit 0.5 mm, 1 mm, 2 mm et 3 mm. Ces caractéristiques incluent le nombre de jours secs, le nombre de périodes de sécheresse ainsi que le maximum de jours consécutifs sans précipitation associé à une récurrence de 5 ans. Les résultats sont présentés pour des moyennes annuelles et saisonnières. L'erreur de performance est évaluée en comparant le MRCC5 piloté par ERA-Interim aux données d'analyses du GPCP pour le climat présent (1997-2008). L'erreur due aux conditions aux frontières c'est-à-dire les erreurs de pilotage du MRCC5, soit par CanESM2 et par ERA-Interim ainsi que l'évaluation de la valeur ajoutée du MRCC5 face au CanESM2 sont également analysées. L'analyse de ces caractéristiques est également faite dans un contexte de climat changeant pour deux périodes futures, soit 2041-2070 et 2071-2100 à l'aide du MRCC5 piloté par le modèle de circulation générale CanESM2 de même que par le modèle CanESM2 sous le scénario RCP 4.5. Les résultats suggèrent que le MRCC5 piloté par ERA-Interim a tendance à surestimer la moyenne annuelle du nombre de jours secs ainsi que le maximum de jours consécutifs sans précipitation associé à une récurrence de 5 ans dans la plupart des régions de l'Afrique et une tendance à sous-estimer le nombre de périodes de sécheresse. En général, l'erreur de performance est plus importante que l'erreur due aux conditions aux frontières pour les différentes caractéristiques de périodes de sécheresse. Pour les régions équatoriales, les changements appréhendés par le MRCC5 piloté par CanESM2 pour les différentes caractéristiques de périodes de sécheresse et pour deux périodes futures (2041-2070 et 2071-2100), suggèrent une augmentation significatives du nombre de jours secs ainsi que du maximum de jours consécutifs sans précipitation associé à une récurrence de 5 ans. Une diminution significative du nombre de périodes de sécheresse est aussi prévue.\ud ______________________________________________________________________________ \ud MOTS-CLÉS DE L’AUTEUR : Modèle Régional du Climat, Changement climatique, Jours secs, Nombre de périodes de sécheresse, Événement de faible récurrence, Afriqu