5WVO

Crystal structure of DNMT1 RFTS domain in complex with K18/K23 mono-ubiquitylated histone H3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance

Ishiyama, S.Nishiyama, A.Saeki, Y.Moritsugu, K.Morimoto, D.Yamaguchi, L.Arai, N.Matsumura, R.Kawakami, T.Mishima, Y.Hojo, H.Shimamura, S.Ishikawa, F.Tajima, S.Tanaka, K.Ariyoshi, M.Shirakawa, M.Ikeguchi, M.Kidera, A.Suetake, I.Arita, K.Nakanishi, M.

(2017) Mol Cell 68: 350-360.e7

  • DOI: https://doi.org/10.1016/j.molcel.2017.09.037
  • Primary Citation of Related Structures:  
    5WVO

  • PubMed Abstract: 

    The proper location and timing of Dnmt1 activation are essential for DNA methylation maintenance. We demonstrate here that Dnmt1 utilizes two-mono-ubiquitylated histone H3 as a unique ubiquitin mark for its recruitment to and activation at DNA methylation sites. The crystal structure of the replication foci targeting sequence (RFTS) of Dnmt1 in complex with H3-K18Ub/23Ub reveals striking differences to the known ubiquitin-recognition structures. The two ubiquitins are simultaneously bound to the RFTS with a combination of canonical hydrophobic and atypical hydrophilic interactions. The C-lobe of RFTS, together with the K23Ub surface, also recognizes the N-terminal tail of H3. The binding of H3-K18Ub/23Ub results in spatial rearrangement of two lobes in the RFTS, suggesting the opening of its active site. Actually, incubation of Dnmt1 with H3-K18Ub/23Ub increases its catalytic activity in vitro. Our results therefore shed light on the essential role of a unique ubiquitin-binding module in DNA methylation maintenance.


  • Organizational Affiliation

    Structure Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ubiquitin
A, B
76Homo sapiensMutation(s): 1 
Gene Names: RPS27AUBA80UBCEP1
UniProt & NIH Common Fund Data Resources
Find proteins for P62979 (Homo sapiens)
Explore P62979 
Go to UniProtKB:  P62979
PHAROS:  P62979
GTEx:  ENSG00000143947 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP62979
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DNA (cytosine-5)-methyltransferase 1250Homo sapiensMutation(s): 0 
Gene Names: DNMT1AIMCXXC9DNMT
EC: 2.1.1.37
UniProt & NIH Common Fund Data Resources
Find proteins for P26358 (Homo sapiens)
Explore P26358 
Go to UniProtKB:  P26358
PHAROS:  P26358
GTEx:  ENSG00000130816 
Entity Groups  
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UniProt GroupP26358
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Histone H3.137Homo sapiensMutation(s): 2 
Gene Names: 
UniProt & NIH Common Fund Data Resources
Find proteins for P68431 (Homo sapiens)
Explore P68431 
Go to UniProtKB:  P68431
PHAROS:  P68431
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP68431
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth C]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.362α = 90
b = 198.779β = 90
c = 76.904γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
JST PRESTOJapan--

Revision History  (Full details and data files)

  • Version 1.0: 2017-11-15
    Type: Initial release
  • Version 1.1: 2023-11-22
    Changes: Data collection, Database references, Refinement description