spacer
spacer

PDBsum entry 2a1r
Go to PDB code: 
protein dna_rna Protein-protein interface(s) links
Hydrolase/RNA PDB id
2a1r

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chain
300 a.a. *
DNA/RNA
Waters ×153
* Residue conservation analysis
PDB id:
2a1r
Name: Hydrolase/RNA
Title: Crystal structure of parn nuclease domain
Structure: 5'-r( Ap Ap A)-3'. Chain: c, d. Engineered: yes. Poly(a)-specific ribonuclease parn. Chain: a, b. Fragment: parn(1-430). Synonym: polyadenylate-specific ribonuclease, deadenylating nuclease, deadenylation nuclease, parn. Engineered: yes
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: parn. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
2.60Å     R-factor:   0.219     R-free:   0.236
Authors: M.Wu,H.Song
Key ref:
M.Wu et al. (2005). Structural insight into poly(A) binding and catalytic mechanism of human PARN. EMBO J, 24, 4082-4093. PubMed id: 16281054 DOI: 10.1038/sj.emboj.7600869
Date:
21-Jun-05     Release date:   20-Dec-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O95453  (PARN_HUMAN) -  Poly(A)-specific ribonuclease PARN from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		639 a.a.
300 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

DNA/RNA chains
  A-A-A 3 bases
  A-A-A 3 bases

 Enzyme reactions 
   Enzyme class: E.C.3.1.13.4  - poly(A)-specific ribonuclease.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Exonucleolytic cleavage of poly(A) to 5'-AMP.

 

 
DOI no: 10.1038/sj.emboj.7600869 EMBO J 24:4082-4093 (2005)
PubMed id: 16281054  
 
 
Structural insight into poly(A) binding and catalytic mechanism of human PARN.
M.Wu, M.Reuter, H.Lilie, Y.Liu, E.Wahle, H.Song.
 
  ABSTRACT  
 
Poly(A)-specific ribonuclease (PARN) is a processive, poly(A)-specific 3' exoribonuclease. The crystal structure of C-terminal truncated human PARN determined in two states (free and RNA-bound forms) reveals that PARNn is folded into two domains, an R3H domain and a nuclease domain similar to those of Pop2p and epsilon186. The high similarity of the active site structures of PARNn and epsilon186 suggests that they may have a similar catalytic mechanism. PARNn forms a tight homodimer, with the R3H domain of one subunit partially enclosing the active site of the other subunit and poly(A) bound in a deep cavity of its nuclease domain in a sequence-nonspecific manner. The R3H domain and, possibly, the cap-binding domain are involved in poly(A) binding but these domains alone do not appear to contribute to poly(A) specificity. Mutations disrupting dimerization abolish both the enzymatic and RNA-binding activities, suggesting that the PARN dimer is a structural and functional unit. The cap-binding domain may act in concert with the R3H domain to amplify the processivity of PARN.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Structures of PARNn in free and RNA-bound forms. (A) Stereo diagram of 2.6 Å simulated annealing (SA) omit map contoured at 2 covering the bound poly(A) in the PARNn-RNA complex. The last three nucleotides are shown in stick model. (B) A ribbon diagram of the PARNn-RNA complex. The two molecules are shown in yellow and green, respectively. Nucleotides are shown in stick model. 3, 4 and 5 are labeled in (B, C). (C) Superimposition of the PARNn-RNA complex with native PARNn. The color coding for the PARNn-RNA complex is as in (B). The two molecules (chain A and chain B) of native PARNn are highlighted with dark green and orange, respectively. Nucleotides are shown in stick model. 		Figure 2.
Figure 2 Comparison of PARNn with other members of the DEDD family. (A) Structural comparison of the nuclease domain of PARNn with those of epsilon 186 and Pop2p. The DEDD core domains are colored yellow, cyan and green for PARN, epsilon 186 and Pop2p, respectively, with the rest of the molecules colored in pale gray. Bound nucleotides are shown in stick model. (B) Structures of the active sites of PARNn, epsilon 186 of Pol III and the klenow fragment of Pol I. Bound nucleotides are shown in stick model, catalytic residues in ball-and-stick model and metal ions in CPK model colored with magenta. (C) Solvent-accessible and electrostatic potential of PARNn colored from blue (basic) to red (acidic). For simplicity, only one subunit is shown. Left panel: the side view of the electrostatic potential surface. Right panel: the top view of the surface rotated about 90° around y axis relative to the view in the left panel.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2005, 24, 4082-4093) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20854710 W.Yang (2011).
Nucleases: diversity of structure, function and mechanism.
  Q Rev Biophys, 44, 1.  
21317904 Y.Y.Hsiao, C.C.Yang, C.L.Lin, J.L.Lin, Y.Duh, and H.S.Yuan (2011).
Structural basis for RNA trimming by RNase T in stable RNA 3'-end maturation.
  Nat Chem Biol, 7, 236-243.
PDB codes: 3ngy 3ngz 3nh0 3nh1 3nh2
20379136 M.A.Cevher, X.Zhang, S.Fernandez, S.Kim, J.Baquero, P.Nilsson, S.Lee, A.Virtanen, and F.E.Kleiman (2010).
Nuclear deadenylation/polyadenylation factors regulate 3' processing in response to DNA damage.
  EMBO J, 29, 1674-1687.  
20144953 M.Wydro, A.Bobrowicz, R.J.Temperley, R.N.Lightowlers, and Z.M.Chrzanowska-Lightowlers (2010).
Targeting of the cytosolic poly(A) binding protein PABPC1 to mitochondria causes mitochondrial translation inhibition.
  Nucleic Acids Res, 38, 3732-3742.  
19901024 N.Henriksson, P.Nilsson, M.Wu, H.Song, and A.Virtanen (2010).
Recognition of adenosine residues by the active site of poly(A)-specific ribonuclease.
  J Biol Chem, 285, 163-170.  
20065043 X.Piao, X.Zhang, L.Wu, and J.G.Belasco (2010).
CCR4-NOT deadenylates mRNA associated with RNA-induced silencing complexes in human cells.
  Mol Cell Biol, 30, 1486-1494.  
19828319 F.Mauxion, C.Y.Chen, B.Séraphin, and A.B.Shyu (2009).
BTG/TOB factors impact deadenylases.
  Trends Biochem Sci, 34, 640-647.  
19459940 G.J.He, A.Zhang, W.F.Liu, Y.Cheng, and Y.B.Yan (2009).
Conformational stability and multistate unfolding of poly(A)-specific ribonuclease.
  FEBS J, 276, 2849-2860.  
19307292 K.R.Andersen, A.T.Jonstrup, L.B.Van, and D.E.Brodersen (2009).
The activity and selectivity of fission yeast Pop2p are affected by a high affinity for Zn2+ and Mn2+ in the active site.
  RNA, 15, 850-861.
PDB codes: 3g0z 3g10
19276069 M.Horiuchi, K.Takeuchi, N.Noda, N.Muroya, T.Suzuki, T.Nakamura, J.Kawamura-Tsuzuku, K.Takahasi, T.Yamamoto, and F.Inagaki (2009).
Structural Basis for the Antiproliferative Activity of the Tob-hCaf1 Complex.
  J Biol Chem, 284, 13244-13255.
PDB code: 2d5r
19217398 M.Wu, P.Nilsson, N.Henriksson, A.Niedzwiecka, M.K.Lim, Z.Cheng, K.Kokkoris, A.Virtanen, and H.Song (2009).
Structural basis of m(7)GpppG binding to poly(A)-specific ribonuclease.
  Structure, 17, 276-286.
PDB code: 3d45
18981218 Y.Y.Hsiao, A.Nakagawa, Z.Shi, S.Mitani, D.Xue, and H.S.Yuan (2009).
Crystal structure of CRN-4: implications for domain function in apoptotic DNA degradation.
  Mol Cell Biol, 29, 448-457.
PDB codes: 3cg7 3cm5 3cm6
18334997 A.C.Goldstrohm, and M.Wickens (2008).
Multifunctional deadenylase complexes diversify mRNA control.
  Nat Rev Mol Cell Biol, 9, 337-344.  
18252771 N.Mirkin, D.Fonseca, S.Mohammed, M.A.Cevher, J.L.Manley, and F.E.Kleiman (2008).
The 3' processing factor CstF functions in the DNA repair response.
  Nucleic Acids Res, 36, 1792-1804.  
18641416 T.Nagata, S.Suzuki, R.Endo, M.Shirouzu, T.Terada, M.Inoue, T.Kigawa, N.Kobayashi, P.Güntert, A.Tanaka, Y.Hayashizaki, Y.Muto, and S.Yokoyama (2008).
The RRM domain of poly(A)-specific ribonuclease has a noncanonical binding site for mRNA cap analog recognition.
  Nucleic Acids Res, 36, 4754-4767.
PDB code: 2rok
17452359 A.T.Jonstrup, K.R.Andersen, L.B.Van, and D.E.Brodersen (2007).
The 1.4-A crystal structure of the S. pombe Pop2p deadenylase subunit unveils the configuration of an active enzyme.
  Nucleic Acids Res, 35, 3153-3164.
PDB code: 2p51
17545151 C.Bönisch, C.Temme, B.Moritz, and E.Wahle (2007).
Degradation of hsp70 and other mRNAs in Drosophila via the 5' 3' pathway and its regulation by heat shock.
  J Biol Chem, 282, 21818-21828.  
17189683 J.A.Worrall, and B.F.Luisi (2007).
Information available at cut rates: structure and mechanism of ribonucleases.
  Curr Opin Struct Biol, 17, 128-137.  
17785461 P.Nilsson, N.Henriksson, A.Niedzwiecka, N.A.Balatsos, K.Kokkoris, J.Eriksson, and A.Virtanen (2007).
A multifunctional RNA recognition motif in poly(A)-specific ribonuclease with cap and poly(A) binding properties.
  J Biol Chem, 282, 32902-32911.  
17437714 Y.Zuo, H.Zheng, Y.Wang, M.Chruszcz, M.Cymborowski, T.Skarina, A.Savchenko, A.Malhotra, and W.Minor (2007).
Crystal structure of RNase T, an exoribonuclease involved in tRNA maturation and end turnover.
  Structure, 15, 417-428.
PDB codes: 2f96 2is3
17052452 J.H.Kim, and J.D.Richter (2006).
Opposing polymerase-deadenylase activities regulate cytoplasmic polyadenylation.
  Mol Cell, 24, 173-183.  
17135487 J.M.Kupsco, M.J.Wu, W.F.Marzluff, R.Thapar, and R.J.Duronio (2006).
Genetic and biochemical characterization of Drosophila Snipper: A promiscuous member of the metazoan 3'hExo/ERI-1 family of 3' to 5' exonucleases.
  RNA, 12, 2103-2117.  
16317009 N.A.Balatsos, P.Nilsson, C.Mazza, S.Cusack, and A.Virtanen (2006).
Inhibition of mRNA deadenylation by the nuclear cap binding complex (CBC).
  J Biol Chem, 281, 4517-4522.  
16882719 S.F.Midtgaard, J.Assenholt, A.T.Jonstrup, L.B.Van, T.H.Jensen, and D.E.Brodersen (2006).
Structure of the nuclear exosome component Rrp6p reveals an interplay between the active site and the HRDC domain.
  Proc Natl Acad Sci U S A, 103, 11898-11903.
PDB codes: 2hbj 2hbk 2hbl 2hbm
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

spacer
spacer