4mzh | pdb_00004mzh

Crystal structure of human Spindlin1 bound to histone H3(K4me3-R8me2s) peptide

spinqualitylabelsall models 4mzh, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mzh is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG NonStd Res: 2MR, M3L Related: 4mzf, 4mzg Gene: SPIN1, OCR, SPIN (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SPIN1_HUMAN] May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity). Publication Abstract from PubMed 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/beta-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. Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1.,Su X, Zhu G, Ding X, Lee SY, Dou Y, Zhu B, Wu W, Li H Genes Dev. 2014 Mar 15;28(6):622-36. doi: 10.1101/gad.233239.113. Epub 2014 Mar, 3. PMID:24589551 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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