ISDA: 4MZF

Deposition Date 2013-09-30

Release Date 2014-03-26

Last Version Date 2025-03-26

Entry Detail

PDB ID:

4MZF

Keywords:

GENE REGULATION

Title:

Crystal structure of human Spindlin1 bound to histone H3(K4me3-R8me2a) peptide

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Expression System(s):

Escherichia coli

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

2.10 Å

R-Value Free:

0.25

R-Value Work:

0.20

R-Value Observed:

0.20

Space Group:

P 21 21 2

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Peptide from Histone H3.2
Gene (Uniprot):H3C15, H3C14, H3C13
Chain IDs:A
Chain Length:9
Number of Molecules:1
Biological Source:Homo sapiens

UniProt ID:Q71DI3

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Spindlin-1
Gene (Uniprot):SPIN1
Chain IDs:B
Chain Length:224
Number of Molecules:1
Biological Source:Homo sapiens

UniProt ID:Q9Y657 Pfam ID:PF02513

Modified Residue

Compound ID	Chain ID	Parent Comp ID	Details	2D Image
DA2	A	ARG	NG,NG-DIMETHYL-L-ARGININE
M3L	A	LYS	N-TRIMETHYLLYSINE

Ligand Molecules

Primary Citation

Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1

Su, X, Zhu, G, Ding, X, Lee, S.Y, Dou, Y, Zhu, B, Wu, W, Li, H.Show

Genes Dev. 28 622 636 (2014)

PMID: 24589551 DOI: 10.1101/gad.233239.113

Abstact

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.

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Primary Citation of related structures

Abstact

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