4MZF
Crystal structure of human Spindlin1 bound to histone H3(K4me3-R8me2a) peptide
Summary for 4MZF
| Entry DOI | 10.2210/pdb4mzf/pdb |
| Related | 4MZG 4MZH |
| Descriptor | Peptide from Histone H3.2, Spindlin-1, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | wnt signal, histone h3, nuclear, gene regulation |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus: Q71DI3 Q9Y657 |
| Total number of polymer chains | 2 |
| Total formula weight | 26837.35 |
| Authors | |
| Primary citation | Su, X.,Zhu, G.,Ding, X.,Lee, S.Y.,Dou, Y.,Zhu, B.,Wu, W.,Li, H. Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1 Genes Dev., 28:622-636, 2014 Cited by PubMed Abstract: Histone modification patterns and their combinatorial readout have emerged as a fundamental mechanism for epigenetic regulation. Here we characterized Spindlin1 as a histone effector that senses a cis-tail histone H3 methylation pattern involving trimethyllysine 4 (H3K4me3) and asymmetric dimethylarginine 8 (H3R8me2a) marks. Spindlin1 consists of triple tudor-like Spin/Ssty repeats. Cocrystal structure determination established concurrent recognition of H3K4me3 and H3R8me2a by Spin/Ssty repeats 2 and 1, respectively. Both H3K4me3 and H3R8me2a are recognized using an "insertion cavity" recognition mode, contributing to a methylation state-specific layer of regulation. In vivo functional studies suggest that Spindlin1 activates Wnt/β-catenin signaling downstream from protein arginine methyltransferase 2 (PRMT2) and the MLL complex, which together are capable of generating a specific H3 "K4me3-R8me2a" pattern. Mutagenesis of Spindlin1 reader pockets impairs activation of Wnt target genes. Taken together, our work connects a histone "lysine-arginine" methylation pattern readout by Spindlin1-to-Wnt signaling at the transcriptional level. PubMed: 24589551DOI: 10.1101/gad.233239.113 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.098 Å) |
Structure validation
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