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Isomerase/biosynthetic protein PDB id
2ey4
Jmol
Contents
Protein chains
329 a.a. *
73 a.a. *
52 a.a. *
Metals
_ZN ×2
Waters ×176
* Residue conservation analysis
PDB id:
2ey4
Name: Isomerase/biosynthetic protein
Title: Crystal structure of a cbf5-nop10-gar1 complex
Structure: Probable tRNA pseudouridine synthase b. Chain: a, b. Synonym: tRNA pseudouridine 55 synthase, psi55 synthase, tr isomerase, tRNA pseudouridylate synthase. Engineered: yes. Small nucleolar rnp similar to gar1. Chain: c, d. Engineered: yes. Ribosome biogenesis protein nop10.
Source: Pyrococcus furiosus. Organism_taxid: 2261. Gene: trub. Expressed in: escherichia coli. Expression_system_taxid: 562. Organism_taxid: 186497. Strain: dsm 3638. Expression_system_taxid: 562
Biol. unit: Trimer (from PQS)
Resolution:
2.11Å     R-factor:   0.211     R-free:   0.255
Authors: R.Rashid,B.Liang,H.Li,Southeast Collaboratory For Structural (Secsg)
Key ref:
R.Rashid et al. (2006). Crystal structure of a Cbf5-Nop10-Gar1 complex and implications in RNA-guided pseudouridylation and dyskeratosis congenita. Mol Cell, 21, 249-260. PubMed id: 16427014 DOI: 10.1016/j.molcel.2005.11.017
Date:
09-Nov-05     Release date:   24-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q7LWY0  (TRUB_PYRFU) -  Probable tRNA pseudouridine synthase B
Seq:
Struc:
340 a.a.
329 a.a.
Protein chains
Pfam   ArchSchema ?
Q8U029  (Q8U029_PYRFU) -  Small nucleolar rnp gar1-like protein
Seq:
Struc:
104 a.a.
73 a.a.
Protein chains
Pfam   ArchSchema ?
Q8U1R4  (NOP10_PYRFU) -  Ribosome biogenesis protein Nop10
Seq:
Struc:
60 a.a.
52 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.5.4.99.25  - tRNA pseudouridine(55) synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: tRNA uridine55 = tRNA pseudouridine55
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     ribonucleoprotein complex   2 terms 
  Biological process     ribosome biogenesis   7 terms 
  Biochemical function     isomerase activity     4 terms  

 

 
DOI no: 10.1016/j.molcel.2005.11.017 Mol Cell 21:249-260 (2006)
PubMed id: 16427014  
 
 
Crystal structure of a Cbf5-Nop10-Gar1 complex and implications in RNA-guided pseudouridylation and dyskeratosis congenita.
R.Rashid, B.Liang, D.L.Baker, O.A.Youssef, Y.He, K.Phipps, R.M.Terns, M.P.Terns, H.Li.
 
  ABSTRACT  
 
H/ACA RNA-protein complexes, comprised of four proteins and an H/ACA guide RNA, modify ribosomal and small nuclear RNAs. The H/ACA proteins are also essential components of telomerase in mammals. Cbf5 is the H/ACA protein that catalyzes isomerization of uridine to pseudouridine in target RNAs. Mutations in human Cbf5 (dyskerin) lead to dyskeratosis congenita. Here, we describe the 2.1 A crystal structure of a specific complex of three archaeal H/ACA proteins, Cbf5, Nop10, and Gar1. Cbf5 displays structural properties that are unique among known pseudouridine synthases and are consistent with its distinct function in RNA-guided pseudouridylation. We also describe the previously unknown structures of both Nop10 and Gar1 and the structural basis for their essential roles in pseudouridylation. By using information from related structures, we have modeled the entire ribonucleoprotein complex including both guide and substrate RNAs. We have also identified a dyskeratosis congenita mutation cluster site within a modeled dyskerin structure.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Comparison of Cbf5 to Regions of TruB and ArcTGT Involved in RNA Binding
Figure 6.
Figure 6. Structural Model of Fully Assembled H/ACA RNP
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 21, 249-260) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21108865 B.Liang, and H.Li (2011).
Structures of ribonucleoprotein particle modification enzymes.
  Q Rev Biophys, 44, 95.  
21241452 B.W.Gu, J.M.Fan, M.Bessler, and P.J.Mason (2011).
Accelerated hematopoietic stem cell aging in a mouse model of dyskeratosis congenita responds to antioxidant treatment.
  Aging Cell, 10, 338-348.  
20008900 C.Trahan, C.Martel, and F.Dragon (2010).
Effects of dyskeratosis congenita mutations in dyskerin, NHP2 and NOP10 on assembly of H/ACA pre-RNPs.
  Hum Mol Genet, 19, 825-836.  
19917616 T.Hamma, and A.R.Ferré-D'Amaré (2010).
The box H/ACA ribonucleoprotein complex: interplay of RNA and protein structures in post-transcriptional RNA modification.
  J Biol Chem, 285, 805-809.  
20227365 T.Kiss, E.Fayet-Lebaron, and B.E.Jády (2010).
Box H/ACA small ribonucleoproteins.
  Mol Cell, 37, 597-606.  
19835419 B.Ashbridge, A.Orte, J.A.Yeoman, M.Kirwan, T.Vulliamy, I.Dokal, D.Klenerman, and S.Balasubramanian (2009).
Single-molecule analysis of the human telomerase RNA.dyskerin interaction and the effect of dyskeratosis congenita mutations.
  Biochemistry, 48, 10858-10865.  
19478803 B.Liang, J.Zhou, E.Kahen, R.M.Terns, M.P.Terns, and H.Li (2009).
Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA.
  Nat Struct Mol Biol, 16, 740-746.
PDB codes: 3hjw 3hjy
19744324 J.Donovan, and P.R.Copeland (2009).
Evolutionary history of selenocysteine incorporation from the perspective of SECIS binding proteins.
  BMC Evol Biol, 9, 229.  
19391112 J.He, B.W.Gu, J.Ge, Y.Mochizuki, M.Bessler, and P.J.Mason (2009).
Variable expression of Dkc1 mutations in mice.
  Genesis, 47, 366-373.  
19103757 J.R.Zamudio, B.Mittra, A.Chattopadhyay, J.A.Wohlschlegel, N.R.Sturm, and D.A.Campbell (2009).
Trypanosoma brucei spliced leader RNA maturation by the cap 1 2'-O-ribose methyltransferase and SLA1 H/ACA snoRNA pseudouridine synthase complex.
  Mol Cell Biol, 29, 1202-1211.  
  19419704 M.Kirwan, and I.Dokal (2009).
Dyskeratosis congenita, stem cells and telomeres.
  Biochim Biophys Acta, 1792, 371-379.  
19734544 P.N.Grozdanov, N.Fernandez-Fuentes, A.Fiser, and U.T.Meier (2009).
Pathogenic NAP57 mutations decrease ribonucleoprotein assembly in dyskeratosis congenita.
  Hum Mol Genet, 18, 4546-4551.  
19383767 P.N.Grozdanov, S.Roy, N.Kittur, and U.T.Meier (2009).
SHQ1 is required prior to NAF1 for assembly of H/ACA small nucleolar and telomerase RNPs.
  RNA, 15, 1188-1197.  
18989882 S.Pigullo, E.Pavesi, I.Dianzani, G.Santamaria, J.Svahn, M.Risso, M.T.Van Lint, M.Pillon, A.P.Iori, D.Longoni, U.Ramenghi, M.Lanciotti, and C.Dufour (2009).
NOLA1 gene mutations in acquired aplastic anemia.
  Pediatr Blood Cancer, 52, 376-378.  
18755842 B.Liang, E.J.Kahen, K.Calvin, J.Zhou, M.Blanco, and H.Li (2008).
Long-distance placement of substrate RNA by H/ACA proteins.
  RNA, 14, 2086-2094.  
18178425 H.Li (2008).
Unveiling substrate RNA binding to H/ACA RNPs: one side fits all.
  Curr Opin Struct Biol, 18, 78-85.  
19829749 J.Karijolich, and Y.T.Yu (2008).
Insight into the Protein Components of the Box H/ACA RNP.
  Curr Proteomics, 5, 129-137.  
18054989 K.Collins (2008).
Physiological assembly and activity of human telomerase complexes.
  Mech Ageing Dev, 129, 91-98.  
18212040 K.Kannan, A.D.Nelson, and D.E.Shippen (2008).
Dyskerin is a component of the Arabidopsis telomerase RNP required for telomere maintenance.
  Mol Cell Biol, 28, 2332-2341.  
18448671 L.Tang, A.Sahasranaman, J.Jakovljevic, E.Schleifman, and J.L.Woolford (2008).
Interactions among Ytm1, Erb1, and Nop7 required for assembly of the Nop7-subcomplex in yeast preribosomes.
  Mol Biol Cell, 19, 2844-2856.  
18005359 M.Kirwan, and I.Dokal (2008).
Dyskeratosis congenita: a genetic disorder of many faces.
  Clin Genet, 73, 103-112.  
18539024 R.Ishitani, S.Yokoyama, and O.Nureki (2008).
Structure, dynamics, and function of RNA modification enzymes.
  Curr Opin Struct Biol, 18, 330-339.  
18057229 R.Machado-Pinilla, I.Sánchez-Pérez, J.R.Murguía, L.Sastre, and R.Perona (2008).
A dyskerin motif reactivates telomerase activity in X-linked dyskeratosis congenita and in telomerase-deficient human cells.
  Blood, 111, 2606-2614.  
18304947 S.Muller, F.Leclerc, I.Behm-Ansmant, J.B.Fourmann, B.Charpentier, and C.Branlant (2008).
Combined in silico and experimental identification of the Pyrococcus abyssi H/ACA sRNAs and their target sites in ribosomal RNAs.
  Nucleic Acids Res, 36, 2459-2475.  
18523010 T.Vulliamy, R.Beswick, M.Kirwan, A.Marrone, M.Digweed, A.Walne, and I.Dokal (2008).
Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita.
  Proc Natl Acad Sci U S A, 105, 8073-8078.  
18332121 W.A.Decatur, and M.N.Schnare (2008).
Different mechanisms for pseudouridine formation in yeast 5S and 5.8S rRNAs.
  Mol Cell Biol, 28, 3089-3100.  
17318225 A.G.Matera, R.M.Terns, and M.P.Terns (2007).
Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs.
  Nat Rev Mol Cell Biol, 8, 209-220.  
17507419 A.J.Walne, T.Vulliamy, A.Marrone, R.Beswick, M.Kirwan, Y.Masunari, F.H.Al-Qurashi, M.Aljurf, and I.Dokal (2007).
Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10.
  Hum Mol Genet, 16, 1619-1629.  
17913752 C.K.Garcia, W.E.Wright, and J.W.Shay (2007).
Human diseases of telomerase dysfunction: insights into tissue aging.
  Nucleic Acids Res, 35, 7406-7416.  
17466623 H.Jin, J.P.Loria, and P.B.Moore (2007).
Solution structure of an rRNA substrate bound to the pseudouridylation pocket of a box H/ACA snoRNA.
  Mol Cell, 26, 205-215.
PDB codes: 2pcv 2pcw
17412831 H.Wu, and J.Feigon (2007).
H/ACA small nucleolar RNA pseudouridylation pockets bind substrate RNA to form three-way junctions that position the target U for modification.
  Proc Natl Acad Sci U S A, 104, 6655-6660.
PDB code: 2p89
17803682 I.Pérez-Arellano, J.Gallego, and J.Cervera (2007).
The PUA domain - a structural and functional overview.
  FEBS J, 274, 4972-4984.  
17663679 J.de la Fuente, and I.Dokal (2007).
Dyskeratosis congenita: advances in the understanding of the telomerase defect and the role of stem cell transplantation.
  Pediatr Transplant, 11, 584-594.  
17574834 K.Ye (2007).
H/ACA guide RNAs, proteins and complexes.
  Curr Opin Struct Biol, 17, 287-292.  
17466622 S.Hur, and R.M.Stroud (2007).
How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruA.
  Mol Cell, 26, 189-203.
PDB codes: 2nqp 2nr0 2nre
17284456 S.L.Reichow, T.Hamma, A.R.Ferré-D'Amaré, and G.Varani (2007).
The structure and function of small nucleolar ribonucleoproteins.
  Nucleic Acids Res, 35, 1452-1464.  
17704128 S.Muller, J.B.Fourmann, C.Loegler, B.Charpentier, and C.Branlant (2007).
Identification of determinants in the protein partners aCBF5 and aNOP10 necessary for the tRNA:Psi55-synthase and RNA-guided RNA:Psi-synthase activities.
  Nucleic Acids Res, 35, 5610-5624.  
17328797 S.Riccardo, G.Tortoriello, E.Giordano, M.Turano, and M.Furia (2007).
The coding/non-coding overlapping architecture of the gene encoding the Drosophila pseudouridine synthase.
  BMC Mol Biol, 8, 15.  
17616598 S.Suzuki, A.Tatsuguchi, E.Matsumoto, M.Kawazoe, T.Kaminishi, M.Shirouzu, Y.Muto, C.Takemoto, and S.Yokoyama (2007).
Structural characterization of the ribosome maturation protein, RimM.
  J Bacteriol, 189, 6397-6406.
PDB code: 2dog
16713250 C.A.Theimer, and J.Feigon (2006).
Structure and function of telomerase RNA.
  Curr Opin Struct Biol, 16, 307-318.  
16931875 C.Normand, R.Capeyrou, S.Quevillon-Cheruel, A.Mougin, Y.Henry, and M.Caizergues-Ferrer (2006).
Analysis of the binding of the N-terminal conserved domain of yeast Cbf5p to a box H/ACA snoRNA.
  RNA, 12, 1868-1882.  
17381300 D.C.Zappulla, and T.R.Cech (2006).
RNA as a flexible scaffold for proteins: yeast telomerase and beyond.
  Cold Spring Harb Symp Quant Biol, 71, 217-224.  
17427287 F.van den Ent, M.Leaver, F.Bendezu, J.Errington, P.de Boer, and J.Löwe (2006).
Dimeric structure of the cell shape protein MreC and its functional implications.
  Mol Microbiol, 62, 1631-1642.
PDB code: 2j5u
16943774 L.Li, and K.Ye (2006).
Crystal structure of an H/ACA box ribonucleoprotein particle.
  Nature, 443, 302-307.
PDB code: 2hvy
16920741 M.Roovers, C.Hale, C.Tricot, M.P.Terns, R.M.Terns, H.Grosjean, and L.Droogmans (2006).
Formation of the conserved pseudouridine at position 55 in archaeal tRNA.
  Nucleic Acids Res, 34, 4293-4301.  
17381322 M.Terns, and R.Terns (2006).
Noncoding RNAs of the H/ACA family.
  Cold Spring Harb Symp Quant Biol, 71, 395-405.  
17135485 N.Kittur, X.Darzacq, S.Roy, R.H.Singer, and U.T.Meier (2006).
Dynamic association and localization of human H/ACA RNP proteins.
  RNA, 12, 2057-2062.  
17085441 S.Hur, R.M.Stroud, and J.Finer-Moore (2006).
Substrate recognition by RNA 5-methyluridine methyltransferases and pseudouridine synthases: a structural perspective.
  J Biol Chem, 281, 38969-38973.  
16647858 U.T.Meier (2006).
How a single protein complex accommodates many different H/ACA RNAs.
  Trends Biochem Sci, 31, 311-315.  
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.