4MZF

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.205 

wwPDB Validation   3D Report Full Report


This is version 1.0 of the entry. See complete history


Literature

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.

(2014) Genes Dev 28: 622-636

  • DOI: https://doi.org/10.1101/gad.233239.113
  • Primary Citation of Related Structures:  
    4MZF, 4MZG, 4MZH

  • 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.


  • Organizational Affiliation

    Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;


Macromolecules

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptide from Histone H3.29Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q71DI3 (Homo sapiens)
Explore Q71DI3 
Go to UniProtKB:  Q71DI3
PHAROS:  Q71DI3
Entity Groups  
UniProt GroupQ71DI3
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Spindlin-1224Homo sapiensMutation(s): 0 
Gene Names: SPIN1OCRSPIN
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y657 (Homo sapiens)
Explore Q9Y657 
Go to UniProtKB:  Q9Y657
PHAROS:  Q9Y657
GTEx:  ENSG00000106723 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y657
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
DA2
Query on DA2
A
L-PEPTIDE LINKINGC8 H18 N4 O2ARG
M3L
Query on M3L
A
L-PEPTIDE LINKINGC9 H21 N2 O2LYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.205 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 120.679α = 90
b = 43.309β = 90
c = 50.15γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-03-26
    Type: Initial release