A binary arginine methylation switch on histone H3 Arginine 2 regulates its interaction with WDR5.

08:00 EDT 24th March 2020 | BioPortfolio

Summary of "A binary arginine methylation switch on histone H3 Arginine 2 regulates its interaction with WDR5."

Histone H3 arginine 2 (H3R2) is post-translationally modified in three different states by "writers" of the protein arginine methyltransferase (PRMT) family. H3R2 methylarginine isoforms include PRMT5-catalyzed monomethylation (me1) and symmetric dimethylation (me2s), and PRMT6-catalyzed me1 and asymmetric dimethylation (me2a). WD-40 repeat-containing protein 5 (WDR5) is an epigenetic "reader" protein that interacts with H3R2. Previous studies suggested that H3R2me2s specified a high-affinity interaction with WDR5. However, our prior biological data prompted the hypothesis that WDR5 may also interact with H3R2me1. Here, using highly accurate quantitative binding analysis combined with high-resolution crystal structures of WDR5 in complex with unmodified (me0) and me1/me2s L-Arginine amino acids and in complex with H3R2me1 peptide, we provide a rigorous biochemical study and address long-standing discrepancies of this important biological interaction. Despite modest structural differences at the binding interface, our study supports an interaction model regulated by a binary arginine methylation switch: H3R2me2a prevents interaction with WDR5, whereas H3R2me0/me1/me2s are equally permissive.


Journal Details

This article was published in the following journal.

Name: Biochemistry
ISSN: 1520-4995


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Medical and Biotech [MESH] Definitions

Enzymes that catalyze the methylation of arginine residues of proteins to yield N-mono- and N,N-dimethylarginine. This enzyme is found in many organs, primarily brain and spleen.

Enzymes that catalyse the removal of methyl groups from LYSINE or ARGININE residues found on HISTONES. Many histone demethylases generally function through an oxidoreductive mechanism.

Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.

An enzyme that activates arginine with its specific transfer RNA. EC

A family of ENZYMES that, in the presence of calcium ion, converts ARGININE to CITRULLINE in proteins.

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