{"doi":"10.1021/acs.biochem.0c00035","title":"A Binary Arginine Methylation Switch on Histone H3 Arginine 2 Regulates Its Interaction with WDR5","abstract":"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 the 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, and -me2s are equally permissive.","journal":"Biochemistry","year":2020,"id":99063,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":369384,"name":"Rajesh K. Harijan","orcid":"0000-0003-1503-5057","position":1,"is_corresponding":false},{"id":488127,"name":"Emmanuel S. Burgos","orcid":"0000-0003-4555-7673","position":2,"is_corresponding":false},{"id":475732,"name":"J.B. Bonanno","orcid":"0000-0003-0863-7826","position":3,"is_corresponding":false},{"id":230350,"name":"Steven C. Almo","orcid":"0000-0003-2591-5234","position":4,"is_corresponding":false},{"id":488128,"name":"David Shechter","orcid":"0000-0001-9388-6004","position":5,"is_corresponding":false},{"id":488126,"name":"Benjamin M. Lorton","orcid":"0000-0002-8553-2078","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T22:37:35.547042Z","pmid":"32207970","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}