3PUF

Crystal structure of human RNase H2 complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutieres syndrome defects.

Figiel, M.Chon, H.Cerritelli, S.M.Cybulska, M.Crouch, R.J.Nowotny, M.

(2011) J Biol Chem 286: 10540-10550

  • DOI: https://doi.org/10.1074/jbc.M110.181974
  • Primary Citation of Related Structures:  
    3PUF

  • PubMed Abstract: 

    RNase H2 cleaves RNA sequences that are part of RNA/DNA hybrids or that are incorporated into DNA, thus, preventing genomic instability and the accumulation of aberrant nucleic acid, which in humans induces Aicardi-Goutières syndrome, a severe autoimmune disorder. The 3.1 Å crystal structure of human RNase H2 presented here allowed us to map the positions of all 29 mutations found in Aicardi-Goutières syndrome patients, several of which were not visible in the previously reported mouse RNase H2. We propose the possible effects of these mutations on the protein stability and function. Bacterial and eukaryotic RNases H2 differ in composition and substrate specificity. Bacterial RNases H2 are monomeric proteins and homologs of the eukaryotic RNases H2 catalytic subunit, which in addition possesses two accessory proteins. The eukaryotic RNase H2 heterotrimeric complex recognizes RNA/DNA hybrids and (5')RNA-DNA(3')/DNA junction hybrids as substrates with similar efficiency, whereas bacterial RNases H2 are highly specialized in the recognition of the (5')RNA-DNA(3') junction and very poorly cleave RNA/DNA hybrids in the presence of Mg(2+) ions. Using the crystal structure of the Thermotoga maritima RNase H2-substrate complex, we modeled the human RNase H2-substrate complex and verified the model by mutational analysis. Our model indicates that the difference in substrate preference stems from the different position of the crucial tyrosine residue involved in substrate binding and recognition.


  • Organizational Affiliation

    Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, Warsaw 02-109, Poland.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ribonuclease H2 subunit A
A, D, G, J, M
A, D, G, J, M, P
302Homo sapiensMutation(s): 0 
Gene Names: RNASEH2ARNASEHIRNHIA
EC: 3.1.26.4
UniProt & NIH Common Fund Data Resources
Find proteins for O75792 (Homo sapiens)
Explore O75792 
Go to UniProtKB:  O75792
PHAROS:  O75792
GTEx:  ENSG00000104889 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO75792
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Ribonuclease H2 subunit B
B, E, H, K, N
B, E, H, K, N, Q
224Homo sapiensMutation(s): 0 
Gene Names: RNASEH2BDLEU8
EC: 3.1.26.4
UniProt & NIH Common Fund Data Resources
Find proteins for Q5TBB1 (Homo sapiens)
Explore Q5TBB1 
Go to UniProtKB:  Q5TBB1
PHAROS:  Q5TBB1
GTEx:  ENSG00000136104 
Entity Groups  
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UniProt GroupQ5TBB1
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Ribonuclease H2 subunit C
C, F, I, L, O
C, F, I, L, O, R
167Homo sapiensMutation(s): 0 
Gene Names: RNASEH2CAYP1
EC: 3.1.26.4
UniProt & NIH Common Fund Data Resources
Find proteins for Q8TDP1 (Homo sapiens)
Explore Q8TDP1 
Go to UniProtKB:  Q8TDP1
PHAROS:  Q8TDP1
GTEx:  ENSG00000172922 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8TDP1
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.206 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 90.068α = 105.9
b = 108.366β = 103.71
c = 114.264γ = 111.42
Software Package:
Software NamePurpose
MAR345dtbdata collection
PHASERphasing
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-12-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-08-29
    Changes: Database references
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Refinement description