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Isomerase/biosynthetic protein/RNA PDB id
2hvy
Jmol
Contents
Protein chains
320 a.a. *
74 a.a. *
53 a.a. *
121 a.a. *
DNA/RNA
Ligands
ATP
Metals
_ZN
Waters ×118
* Residue conservation analysis
PDB id:
2hvy
Name: Isomerase/biosynthetic protein/RNA
Title: Crystal structure of an h/aca box rnp from pyrococcus furios
Structure: H/aca RNA. Chain: e. Engineered: yes. Probable tRNA pseudouridine synthase b. Chain: a. Synonym: tRNA pseudouridine 55 synthase, psi55 synthase, tr isomerase, tRNA pseudouridylate synthase. Engineered: yes. Small nucleolar rnp similar to gar1.
Source: Synthetic: yes. Other_details: derived from afu-46 RNA. Pyrococcus furiosus. Organism_taxid: 2261. Gene: trub. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: gar1. Gene: nop10.
Biol. unit: Pentamer (from PQS)
Resolution:
2.30Å     R-factor:   0.240     R-free:   0.278
Authors: K.Ye
Key ref:
L.Li and K.Ye (2006). Crystal structure of an H/ACA box ribonucleoprotein particle. Nature, 443, 302-307. PubMed id: 16943774 DOI: 10.1038/nature05151
Date:
31-Jul-06     Release date:   12-Sep-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q7LWY0  (TRUB_PYRFU) -  Probable tRNA pseudouridine synthase B
Seq:
Struc: 		340 a.a.
320 a.a.
Protein chain
Pfam   ArchSchema ?
Q8U029  (Q8U029_PYRFU) -  Small nucleolar rnp gar1-like protein
Seq:
Struc: 		104 a.a.
74 a.a.
Protein chain
Pfam   ArchSchema ?
Q8U1R4  (NOP10_PYRFU) -  Ribosome biogenesis protein Nop10
Seq:
Struc: 		60 a.a.
53 a.a.
Protein chain
Pfam   ArchSchema ?
Q8U160  (RL7A_PYRFU) -  50S ribosomal protein L7Ae
Seq:
Struc: 		123 a.a.
121 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain A: 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     intracellular   4 terms 
  Biological process     ribosome biogenesis   8 terms 
  Biochemical function     isomerase activity     5 terms  

 

 
DOI no: 10.1038/nature05151 Nature 443:302-307 (2006)
PubMed id: 16943774  
 
 
Crystal structure of an H/ACA box ribonucleoprotein particle.
L.Li, K.Ye.
 
  ABSTRACT  
 
H/ACA ribonucleoprotein particles (RNPs) are a family of RNA pseudouridine synthases that specify modification sites through guide RNAs. They also participate in eukaryotic ribosomal RNA processing and are a component of vertebrate telomerases. Here we report the crystal structure, at 2.3 A resolution, of an entire archaeal H/ACA RNP consisting of proteins Cbf5, Nop10, Gar1 and L7ae, and a single-hairpin H/ACA RNA, revealing a modular organization of the complex. The RNA upper stem is bound to a composite surface formed by L7ae, Nop10 and Cbf5, and the RNA lower stem and ACA signature motif are bound to the PUA domain of Cbf5, thereby positioning middle guide sequences so that they are primed to pair with substrate RNA. Furthermore, Gar1 may regulate substrate loading and release. The structure rationalizes the consensus structure of H/ACA RNAs, suggests a functional role of each protein, and provides a framework for understanding the mechanism of RNA-guided pseudouridylation, as well as various cellular functions of H/ACA RNP.
 
  Selected figure(s)  
 
Figure 1.
Figure 1: Structure of H/ACA RNP.
a, Sequence and secondary structure of the single-hairpin archaeal H/ACA RNA used in this study. Also shown is a bound cognate substrate RNA, which is, however, not present in the structure. Paired regions are named as P1 and P2 for the lower and upper stems, and PS1 and PS2 for duplexes formed between guide sequences (orange) and substrate RNA (purple), respectively. The modification target is shown as product pseudouridine ( , red). The terminal k-turn and ACA motif are highlighted in red. Every tenth nucleotide is numbered, with prime denoting numbering of the substrate RNA. b, Ribbon representation of the H/ACA RNP structure in front view. c, Side view. Different colours are used for the Cbf5 catalytic domain (dark green), Cbf5 PUA domain (lime green), Nop10 and zinc ion (magenta), L7ae (light blue), Gar1 (cyan), k-turn and ACA motifs (red), guides (orange) and the rest of the RNA (yellow). The same colour coding is used for the other figures. Major secondary structure elements are shown for proteins. The N and C termini are indicated when appropriate. Dots represent disordered chains; star denotes the active site. 		Figure 2.
Figure 2: PUA recognition of the P1 stem and the ACA motif. a, Overall view highlighting the intimate protein contacts along the P1 minor groove. b, The RNA–protein hybrid binding pocket for A58. c, Binding of C59 and A60. Interacting residues are shown in ball-and-stick representation, water as a red sphere, hydrogen bonds as dashed lines, and hydrogen-bonding atoms are coloured as red for oxygen and blue for nitrogen. Interactions are shown in the same manner in Figs 3 and 4. d, Dyskeratosis congenita mutations in the PUA domain, indicated by C spheres, side chains from this structure and residue numbers in dyskerin. Also shown is the RNA enveloped in the 2f[o] - f[c] electron density map at the 1.5 level and the partial RNA-binding surface.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2006, 443, 302-307) 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.  
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.  
19926724 K.T.Gagnon, X.Zhang, G.Qu, S.Biswas, J.Suryadi, B.A.Brown, and E.S.Maxwell (2010).
Signature amino acids enable the archaeal L7Ae box C/D RNP core protein to recognize and bind the K-loop RNA motif.
  RNA, 16, 79-90.  
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
19191354 C.Bertonati, M.Punta, M.Fischer, G.Yachdav, F.Forouhar, W.Zhou, A.P.Kuzin, J.Seetharaman, M.Abashidze, T.A.Ramelot, M.A.Kennedy, J.R.Cort, A.Belachew, J.F.Hunt, L.Tong, G.T.Montelione, and B.Rost (2009).
Structural genomics reveals EVE as a new ASCH/PUA-related domain.
  Proteins, 75, 760-773.
PDB codes: 1zce 2eve 2g2x 2gbs
19322192 E.Fayet-Lebaron, V.Atzorn, Y.Henry, and T.Kiss (2009).
18S rRNA processing requires base pairings of snR30 H/ACA snoRNA to eukaryote-specific 18S sequences.
  EMBO J, 28, 1260-1270.  
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.  
19285445 K.T.Tycowski, M.D.Shu, A.Kukoyi, and J.A.Steitz (2009).
A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles.
  Mol Cell, 34, 47-57.  
19666563 K.Ye, R.Jia, J.Lin, M.Ju, J.Peng, A.Xu, and L.Zhang (2009).
Structural organization of box C/D RNA-guided RNA methyltransferase.
  Proc Natl Acad Sci U S A, 106, 13808-13813.
PDB codes: 3icx 3id5 3id6
19763159 M.S.Scott, F.Avolio, M.Ono, A.I.Lamond, and G.J.Barton (2009).
Human miRNA precursors with box H/ACA snoRNA features.
  PLoS Comput Biol, 5, e1000507.  
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.  
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.  
18986541 I.Myslyuk, T.Doniger, Y.Horesh, A.Hury, R.Hoffer, Y.Ziporen, S.Michaeli, and R.Unger (2008).
Psiscan: a computational approach to identify H/ACA-like and AGA-like non-coding RNA in trypanosomatid genomes.
  BMC Bioinformatics, 9, 471.  
19829749 J.Karijolich, and Y.T.Yu (2008).
Insight into the Protein Components of the Box H/ACA RNP.
  Curr Proteomics, 5, 129-137.  
18539024 R.Ishitani, S.Yokoyama, and O.Nureki (2008).
Structure, dynamics, and function of RNA modification enzymes.
  Curr Opin Struct Biol, 18, 330-339.  
18268104 S.Boulon, N.Marmier-Gourrier, B.Pradet-Balade, L.Wurth, C.Verheggen, B.E.Jády, B.Rothé, C.Pescia, M.C.Robert, T.Kiss, B.Bardoni, A.Krol, C.Branlant, C.Allmang, E.Bertrand, and B.Charpentier (2008).
The Hsp90 chaperone controls the biogenesis of L7Ae RNPs through conserved machinery.
  J Cell Biol, 180, 579-595.  
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.  
17473849 B.M.Lunde, C.Moore, and G.Varani (2007).
RNA-binding proteins: modular design for efficient function.
  Nat Rev Mol Cell Biol, 8, 479-490.  
17889661 C.A.Theimer, B.E.Jády, N.Chim, P.Richard, K.E.Breece, T.Kiss, and J.Feigon (2007).
Structural and functional characterization of human telomerase RNA processing and cajal body localization signals.
  Mol Cell, 27, 869-881.
PDB codes: 2qh2 2qh3 2qh4
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.  
17519961 F.M.Boisvert, S.van Koningsbruggen, J.Navascués, and A.I.Lamond (2007).
The multifunctional nucleolus.
  Nat Rev Mol Cell Biol, 8, 574-585.  
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
17712600 I.Lermontova, V.Schubert, F.Börnke, J.Macas, and I.Schubert (2007).
Arabidopsis CBF5 interacts with the H/ACA snoRNP assembly factor NAF1.
  Plant Mol Biol, 65, 615-626.  
17803682 I.Pérez-Arellano, J.Gallego, and J.Cervera (2007).
The PUA domain - a structural and functional overview.
  FEBS J, 274, 4972-4984.  
17574834 K.Ye (2007).
H/ACA guide RNAs, proteins and complexes.
  Curr Opin Struct Biol, 17, 287-292.  
17855403 O.A.Youssef, R.M.Terns, and M.P.Terns (2007).
Dynamic interactions within sub-complexes of the H/ACA pseudouridylation guide RNP.
  Nucleic Acids Res, 35, 6196-6206.  
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
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.  
17275836 T.J.Santangelo, L.Cubonová, C.L.James, and J.N.Reeve (2007).
TFB1 or TFB2 is sufficient for Thermococcus kodakaraensis viability and for basal transcription in vitro.
  J Mol Biol, 367, 344-357.  
17434535 T.S.Maity, and K.M.Weeks (2007).
A threefold RNA-protein interface in the signal recognition particle gates native complex assembly.
  J Mol Biol, 369, 512-524.  
17381322 M.Terns, and R.Terns (2006).
Noncoding RNAs of the H/ACA family.
  Cold Spring Harb Symp Quant Biol, 71, 395-405.  
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.  
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.