PDBsum entry 4mzf

Gene regulation

PDB id: 4mzf

Contents

Protein chain

203 a.a.

Ligands

ALA-ARG-THR-M3L-GLN-THR-ALA-DA2-LYS

Metals

_MG

_CL ×2

Waters ×113

PDB id:

4mzf

Name:

Gene regulation

Title:

Crystal structure of human spindlin1 bound to histone h3(k4me3-r8me2a) peptide

Structure:

Peptide from histone h3.2. Chain: a. Synonym: histone h3/m, histone h3/o. Engineered: yes. Spindlin-1. Chain: b. Fragment: unp residues 50-262. Synonym: sp1, ovarian cancer-related protein. Engineered: yes

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: spin1, ocr, spin. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.10Å R-factor: 0.205 R-free: 0.255

Authors:

X.Su,X.Ding,H.Li

Key ref:

X.Su et al. (2014). Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1. Genes Dev, 28, 622-636. PubMed id: 24589551 DOI: 10.1101/gad.233239.113

Date:

30-Sep-13 Release date: 26-Mar-14

Protein chain

Q9Y657  (SPIN1_HUMAN) -  Spindlin-1 from Homo sapiens

Seq: 262 a.a.

Struc: 203 a.a.*

* PDB and UniProt seqs differ at 11 residue positions (black crosses)

DOI no: 10.1101/gad.233239.113

Genes Dev 28:622-636 (2014)

PubMed id: 24589551

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

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

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.