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Hydrolase PDB id
2je6
Jmol
Contents
Protein chains
274 a.a. *
234 a.a. *
207 a.a. *
Ligands
1PE
PEG
Metals
_CL
Waters ×398
* Residue conservation analysis
PDB id:
2je6
Name: Hydrolase
Title: Structure of a 9-subunit archaeal exosome
Structure: Exosome complex exonuclease 2. Chain: a. Synonym: rrp42. Engineered: yes. Exosome complex exonuclease 1. Chain: b. Synonym: rrp41. Engineered: yes. Mutation: yes.
Source: Sulfolobus solfataricus. Organism_taxid: 2287. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
1.60Å     R-factor:   0.216     R-free:   0.249
Authors: E.Lorentzen,E.Conti
Key ref:
E.Lorentzen et al. (2007). RNA channelling by the archaeal exosome. EMBO Rep, 8, 470-476. PubMed id: 17380186 DOI: 10.1038/sj.embor.7400945
Date:
15-Jan-07     Release date:   23-Jan-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9UXC0  (ECX2_SULSO) -  Probable exosome complex exonuclease 2
Seq:
Struc: 		275 a.a.
274 a.a.
Protein chain
Pfam   ArchSchema ?
Q9UXC2  (ECX1_SULSO) -  Probable exosome complex exonuclease 1
Seq:
Struc: 		248 a.a.
234 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9UXC4  (ECR1_SULSO) -  Probable exosome complex RNA-binding protein 1
Seq:
Struc: 		249 a.a.
207 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     exosome (RNase complex)   2 terms 
  Biological process     RNA processing   2 terms 
  Biochemical function     hydrolase activity     7 terms  

 

 
DOI no: 10.1038/sj.embor.7400945 EMBO Rep 8:470-476 (2007)
PubMed id: 17380186  
 
 
RNA channelling by the archaeal exosome.
E.Lorentzen, A.Dziembowski, D.Lindner, B.Seraphin, E.Conti.
 
  ABSTRACT  
 
Exosomes are complexes containing 3' --> 5' exoribonucleases that have important roles in processing, decay and quality control of various RNA molecules. Archaeal exosomes consist of a hexameric core of three active RNase PH subunits (ribosomal RNA processing factor (Rrp)41) and three inactive RNase PH subunits (Rrp42). A trimeric ring of subunits with putative RNA-binding domains (Rrp4/cep1 synthetic lethality (Csl)4) is positioned on top of the hexamer on the opposite side to the RNA degrading sites. Here, we present the 1.6 A resolution crystal structure of the nine-subunit exosome of Sulfolobus solfataricus and the 2.3 A structure of this complex bound to an RNA substrate designed to be partly trimmed rather than completely degraded. The RNA binds both at the active site on one side of the molecule and on the opposite side in the narrowest constriction of the central channel. Multiple substrate-binding sites and the entrapment of the substrate in the central channel provide a rationale for the processive degradation of extended RNAs and the stalling of structured RNAs.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Structure of the complete 270 kDa Sulfolobus solfataricus exosome. (A) Two views of the complex, with Rrp41 in blue, Rrp42 in green and Rrp4 in yellow. Manganese ions are shown in cyan. The views are rotated by 90° around the horizontal axis. This figure and all others representing structures were generated with the program PYMOL (http://pymol.sourceforge.net, Warren L. DeLano). (B) View of the S. solfataricus exosome (Rrp4 in yellow, and Rrp41 and Rrp42 in light grey) superposed on the A. fulgidus exosome using the RNase PH cores (Rrp4 in red, Rrp41 and Rrp42 in dark grey). The structures are viewed as in (A), left. The three domains of Rrp4 (N-terminal, S1 and KH) are indicated. (C) View of the S. solfataricus exosome superposed on the human exosome using the RNase PH cores (light grey for S. solfataricus and dark grey for human RNase PH). Ss-Rrp4 is shown in yellow, Hs-Rrp40 in magenta, Hs-Rrp4 in green and Hs-Csl4 in pink. Csl4, cep1 synthetic lethality; Hs, Homo sapiens; Rrp, ribosomal RNA processing factor; Ss, Sulfolobus solfatarious. 		Figure 3.
Figure 3 Metal ions mediate subunit interactions. (A) A close-up view showing the structural manganese (Mn) ion-binding site in the Sulfolobus solfataricus (Ss) exosome, located at the interface between Ss-Rrp41 (blue) and Ss-Rrp4 (yellow). A 2.4 Å resolution 2F[o]-F[c] electron density map contoured at 1 is shown in blue and an anomalous map at 4 Å resolution contoured at 4 is shown in magenta. Residues that coordinate the metal ion are labelled. (B) The equivalent region of the Archaeglobus fulgidus exosome structure showing that the metal ion-binding site found in the S. solfataricus exosome is replaced by a direct salt-bridge (dotted line). (C) Sequence alignment showing that the Rrp41–Rrp4 contacts are probably mediated either by divalent metal ions or by a direct salt bridge in exosomes from different organisms. Sequences included are: S. solfataricus (SULSO), Pyrococcus furiosus (PYRFU), Dictyostelium discoideum (DICDI), A. fulgidus (ARCFU), Saccharomyces cerevisiae (YEAST) and Homo sapiens (HUMAN). Numbers in parentheses denote overall percentage identity of the full-length proteins to the S. solfataricus sequence. D, aspartic acid; E, glutamic acid; K, lysine; Rrp, ribosomal RNA processing factor.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO Rep (2007, 8, 470-476) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21173259 J.Prikryl, M.Rojas, G.Schuster, and A.Barkan (2011).
Mechanism of RNA stabilization and translational activation by a pentatricopeptide repeat protein.
  Proc Natl Acad Sci U S A, 108, 415-420.  
20854710 W.Yang (2011).
Nucleases: diversity of structure, function and mechanism.
  Q Rev Biophys, 44, 1.  
21072062 B.Tsanova, and A.van Hoof (2010).
Poring over exosome structure.
  EMBO Rep, 11, 900-901.  
20445227 C.L.Ng, D.G.Waterman, A.A.Antson, and M.Ortiz-Lombardía (2010).
Structure of the Methanothermobacter thermautotrophicus exosome RNase PH ring.
  Acta Crystallogr D Biol Crystallogr, 66, 522-528.
PDB code: 2wnr
20090900 C.Lu, F.Ding, and A.Ke (2010).
Crystal structure of the S. solfataricus archaeal exosome reveals conformational flexibility in the RNA-binding ring.
  PLoS One, 5, e8739.
PDB code: 3l7z
21072061 H.Malet, M.Topf, D.K.Clare, J.Ebert, F.Bonneau, J.Basquin, K.Drazkowska, R.Tomecki, A.Dziembowski, E.Conti, H.R.Saibil, and E.Lorentzen (2010).
RNA channelling by the eukaryotic exosome.
  EMBO Rep, 11, 936-942.  
20507607 J.S.Luz, C.R.Ramos, M.C.Santos, P.P.Coltri, F.L.Palhano, D.Foguel, N.I.Zanchin, and C.C.Oliveira (2010).
Identification of archaeal proteins that affect the exosome function in vitro.
  BMC Biochem, 11, 22.  
20301164 R.Tomecki, K.Drazkowska, and A.Dziembowski (2010).
Mechanisms of RNA degradation by the eukaryotic exosome.
  Chembiochem, 11, 938-945.  
20392821 S.Hartung, T.Niederberger, M.Hartung, A.Tresch, and K.P.Hopfner (2010).
Quantitative analysis of processive RNA degradation by the archaeal RNA exosome.
  Nucleic Acids Res, 38, 5166-5176.
PDB codes: 3m7n 3m85
19879841 F.Bonneau, J.Basquin, J.Ebert, E.Lorentzen, and E.Conti (2009).
The yeast exosome functions as a macromolecular cage to channel RNA substrates for degradation.
  Cell, 139, 547-559.  
19913477 M.F.Symmons, and B.F.Luisi (2009).
Through ancient rings thread programming strings.
  Structure, 17, 1429-1431.  
19327365 S.Nurmohamed, B.Vaidialingam, A.J.Callaghan, and B.F.Luisi (2009).
Crystal structure of Escherichia coli polynucleotide phosphorylase core bound to RNase E, RNA and manganese: implications for catalytic mechanism and RNA degradosome assembly.
  J Mol Biol, 389, 17-33.
PDB code: 3h1c
18255277 A.Serganov, and D.J.Patel (2008).
Towards deciphering the principles underlying an mRNA recognition code.
  Curr Opin Struct Biol, 18, 120-129.  
18955140 E.Lorentzen, J.Basquin, and E.Conti (2008).
Structural organization of the RNA-degrading exosome.
  Curr Opin Struct Biol, 18, 709-713.  
  18078842 H.Ibrahim, J.Wilusz, and C.J.Wilusz (2008).
RNA recognition by 3'-to-5' exonucleases: the substrate perspective.
  Biochim Biophys Acta, 1779, 256-265.  
19111177 J.C.Greimann, and C.D.Lima (2008).
Reconstitution of RNA exosomes from human and Saccharomyces cerevisiae cloning, expression, purification, and activity assays.
  Methods Enzymol, 448, 185-210.  
18786828 M.Schmid, and T.H.Jensen (2008).
The exosome: a multipurpose RNA-decay machine.
  Trends Biochem Sci, 33, 501-510.  
18353775 M.V.Navarro, C.C.Oliveira, N.I.Zanchin, and B.G.Guimarães (2008).
Insights into the mechanism of progressive RNA degradation by the archaeal exosome.
  J Biol Chem, 283, 14120-14131.
PDB codes: 2pnz 2po0 2po1 2po2
18084187 P.C.Gilligan, and K.Sampath (2008).
Reining in RNA. Workshop on intracellular RNA localization and localized translation.
  EMBO Rep, 9, 22-26.  
18493045 S.L.Zimmer, Z.Fei, and D.B.Stern (2008).
Genome-based analysis of Chlamydomonas reinhardtii exoribonucleases and poly(A) polymerases predicts unexpected organellar and exosomal features.
  Genetics, 179, 125-136.  
18812438 Z.Shi, W.Z.Yang, S.Lin-Chao, K.F.Chak, and H.S.Yuan (2008).
Crystal structure of Escherichia coli PNPase: central channel residues are involved in processive RNA degradation.
  RNA, 14, 2361-2371.
PDB codes: 3cdi 3cdj
17601780 C.M.Arraiano, J.Bamford, H.Brüssow, A.J.Carpousis, V.Pelicic, K.Pflüger, P.Polard, and J.Vogel (2007).
Recent advances in the expression, evolution, and dynamics of prokaryotic genomes.
  J Bacteriol, 189, 6093-6100.  
17942686 H.W.Wang, J.Wang, F.Ding, K.Callahan, M.A.Bratkowski, J.S.Butler, E.Nogales, and A.Ke (2007).
Architecture of the yeast Rrp44 exosome complex suggests routes of RNA recruitment for 3' end processing.
  Proc Natl Acad Sci U S A, 104, 16844-16849.  
17471261 S.Hartung, and K.P.Hopfner (2007).
The exosome, plugged.
  EMBO Rep, 8, 456-457.  
17603538 S.Vanacova, and R.Stefl (2007).
The exosome and RNA quality control in the nucleus.
  EMBO Rep, 8, 651-657.  
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 code is shown on the right.