6OI1
Crystal structure of human WDR5 in complex with monomethyl L-arginine
Summary for 6OI1
| Entry DOI | 10.2210/pdb6oi1/pdb |
| Descriptor | WD repeat-containing protein 5, SULFATE ION, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | methylation, epigenetics, post-translational modification, chromatin, methylarginine, gene regulation |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 34859.47 |
| Authors | Lorton, B.M.,Harijan, R.K.,Burgos, E.,Bonanno, J.B.,Almo, S.C.,Shechter, D. (deposition date: 2019-04-08, release date: 2020-04-01, Last modification date: 2023-10-11) |
| Primary citation | Lorton, B.M.,Harijan, R.K.,Burgos, E.S.,Bonanno, J.B.,Almo, S.C.,Shechter, D. A Binary Arginine Methylation Switch on Histone H3 Arginine 2 Regulates Its Interaction with WDR5. Biochemistry, 59:3696-3708, 2020 Cited by PubMed 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. PubMed: 32207970DOI: 10.1021/acs.biochem.0c00035 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.68 Å) |
Structure validation
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