|Title||Intrinsic protein disorder in histone lysine methylation.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Lazar, T., E. Schad, B. Szabo, T. Horvath, A. Meszaros, P. Tompa, and Á. Tantos|
|Date Published||2016 Jun 30|
UNLABELLED: 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.
|Alternate Journal||Biol. Direct|
|PubMed Central ID||PMC4928265|
Intrinsic protein disorder in histone lysine methylation.