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Hydrolase PDB id
2hxy
Jmol
Contents
Protein chains
376 a.a. *
* Residue conservation analysis
PDB id:
2hxy
Name: Hydrolase
Title: Crystal structure of human apo-eif4aiii
Structure: Probable atp-dependent RNA helicase ddx48. Chain: a, b, c, d. Synonym: dead box protein 48, eukaryotic initiation factor 4a-like nuk-34, nuclear matrix protein 265, hnmp 265, eukaryotic translation initiation factor 4a isoform 3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ddx48, eif4a3, kiaa0111. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
3.30Å     R-factor:   0.275     R-free:   0.308
Authors: J.S.Johansen,G.R.Andersen
Key ref:
C.B.Andersen et al. (2006). Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA. Science, 313, 1968-1972. PubMed id: 16931718 DOI: 10.1126/science.1131981
Date:
04-Aug-06     Release date:   15-Aug-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P38919  (IF4A3_HUMAN) -  Eukaryotic initiation factor 4A-III
Seq:
Struc: 		411 a.a.
376 a.a.
Key:    PfamA domain  Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.3.6.4.13  - Rna helicase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate
ATP
 + H(2)O
 = ADP
 + phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   4 terms 
  Biological process     transport   9 terms 
  Biochemical function     nucleotide binding     10 terms  

 

 
    reference    
 
 
DOI no: 10.1126/science.1131981 Science 313:1968-1972 (2006)
PubMed id: 16931718  
 
 
Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA.
C.B.Andersen, L.Ballut, J.S.Johansen, H.Chamieh, K.H.Nielsen, C.L.Oliveira, J.S.Pedersen, B.Séraphin, H.Le Hir, G.R.Andersen.
 
  ABSTRACT  
 
In higher eukaryotes, a multiprotein exon junction complex is deposited on spliced messenger RNAs. The complex is organized around a stable core, which serves as a binding platform for numerous factors that influence messenger RNA function. Here, we present the crystal structure of a tetrameric exon junction core complex containing the DEAD-box adenosine triphosphatase (ATPase) eukaryotic initiation factor 4AIII (eIF4AIII) bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic. eIF4AIII interacts with the phosphate-ribose backbone of six consecutive nucleotides and prevents part of the bound RNA from being double stranded. The MAGOH and Y14 subunits lock eIF4AIII in a prehydrolysis state, and activation of the ATPase probably requires only modest conformational changes in eIF4AIII motif I.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Structures of the EJC and free eIF4AIII. (A) The EJC viewed from the ATP side (left) and the RNA side (right) with domains 1 and 2 of eIF4AIII colored blue and green, respectively. MLN51 is shown in purple, Y14 in yellow, and MAGOH in red. The dotted line connects the two ordered fragments of MLN51. (B) The open conformation of eIF4AIII with domain 1 in the same orientation as in the left panel of (A). (C) Surface representation of eIF4AIII, in which the three other subunits are shown as C skeletons. Conserved DEAD-box motifs (4) and eIF4AIII specific patches (7) (fig. S1) are mapped. 		Figure 2.
Fig. 2. Intersubunit and RNA contacts within the EJC. (A) Interaction footprint of MAGOH (red) and Y14 (yellow) on eIF4AIII and MLN51. (B) Interaction footprint of eIF4AIII (green) and MLN51 (purple) on MAGOH-Y14. (B) is rotated 180° relative to (A) around a vertical axis located between MAGOH-Y14 and eIF4AIII-MLN51. Residue numbers in MLN51, Y14, or MAGOH are preceded by m, y, or a, respectively. (C) Interaction of the C-terminal (C-term) residues of MAGOH with conserved motifs at the ATP binding site. Water molecules are marked w. (D) Packing of the linker for eIF4AIII domains 1 and 2 between MAGOH and motifs I and III at the ATP site. (E) Stereoview of the RNA bound to eIF4AIII with MLN51 forming the 5' boundary of the binding pocket. Motifs Ia, Ib, IV, and V in eIF4AIII contribute to the RNA binding pocket. Residues shown in gray also participate in RNA binding but are not part of the DEAD-box motifs. Amino acid residues are labeled (28).
 
  The above figures are reprinted by permission from the AAAs: Science (2006, 313, 1968-1972) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21428949 D.Klostermeier (2011).
Single-molecule FRET reveals nucleotide-driven conformational changes in molecular machines and their link to RNA unwinding and DNA supercoiling.
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RNA helicases at work: binding and rearranging.
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21321231 F.Li, J.Herrera, S.Zhou, D.A.Maslov, and L.Simpson (2011).
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21391900 J.Strohmeier, I.Hertel, U.Diederichsen, M.G.Rudolph, and D.Klostermeier (2011).
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21062831 M.Hilbert, F.Kebbel, A.Gubaev, and D.Klostermeier (2011).
eIF4G stimulates the activity of the DEAD box protein eIF4A by a conformational guidance mechanism.
  Nucleic Acids Res, 39, 2260-2270.  
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20946982 J.Y.Roignant, and J.E.Treisman (2010).
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Three conformational snapshots of the hepatitis C virus NS3 helicase reveal a ratchet translocation mechanism.
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Comparative structural analysis of human DEAD-box RNA helicases.
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19474341 A.R.Karow, and D.Klostermeier (2009).
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19716792 M.E.Budiman, J.L.Bubenik, A.C.Miniard, L.M.Middleton, C.A.Gerber, A.Cash, and D.M.Driscoll (2009).
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19710183 M.G.Rudolph, and D.Klostermeier (2009).
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The mechanism of ATP-dependent RNA unwinding by DEAD box proteins.
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19700770 M.N.Murphy, P.Gong, K.Ralto, L.Manelyte, N.J.Savery, and K.Theis (2009).
An N-terminal clamp restrains the motor domains of the bacterial transcription-repair coupling factor Mfd.
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19002498 M.Singh, K.K.Srivastava, and S.M.Bhattacharya (2009).
Molecular cloning and characterization of a novel immunoreactive ATPase/RNA helicase in human filarial parasite Brugia malayi.
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Disassembly of exon junction complexes by PYM.
  Cell, 137, 536-548.  
19478851 N.H.Gehring, S.Lamprinaki, M.W.Hentze, and A.E.Kulozik (2009).
The hierarchy of exon-junction complex assembly by the spliceosome explains key features of mammalian nonsense-mediated mRNA decay.
  PLoS Biol, 7, e1000120.  
19625490 N.T.Uyen, S.Y.Park, J.W.Choi, H.J.Lee, K.Nishi, and J.S.Kim (2009).
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19153607 P.G.Loh, H.S.Yang, M.A.Walsh, Q.Wang, X.Wang, Z.Cheng, D.Liu, and H.Song (2009).
Structural basis for translational inhibition by the tumour suppressor Pdcd4.
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19244245 R.Collins, T.Karlberg, L.Lehtiö, P.Schütz, S.van den Berg, L.G.Dahlgren, M.Hammarström, J.Weigelt, and H.Schüler (2009).
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  J Biol Chem, 284, 10296-10300.
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Inhibition of nonsense-mediated mRNA decay by the natural product pateamine A through eukaryotic initiation factor 4AIII.
  J Biol Chem, 284, 23613-23621.  
18573084 A.M.Pyle (2008).
Translocation and unwinding mechanisms of RNA and DNA helicases.
  Annu Rev Biophys, 37, 317-336.  
18255277 A.Serganov, and D.J.Patel (2008).
Towards deciphering the principles underlying an mRNA recognition code.
  Curr Opin Struct Biol, 18, 120-129.  
18184816 B.Theissen, A.R.Karow, J.Köhler, A.Gubaev, and D.Klostermeier (2008).
Cooperative binding of ATP and RNA induces a closed conformation in a DEAD box RNA helicase.
  Proc Natl Acad Sci U S A, 105, 548-553.  
19008861 D.Luo, T.Xu, R.P.Watson, D.Scherer-Becker, A.Sampath, W.Jahnke, S.S.Yeong, C.H.Wang, S.P.Lim, A.Strongin, S.G.Vasudevan, and J.Lescar (2008).
Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 protein.
  EMBO J, 27, 3209-3219.
PDB codes: 2jlq 2jlr 2jls 2jlu 2jlv 2jlw 2jlx 2jly 2jlz
18952819 D.M.Mishler, A.B.Christ, and J.A.Steitz (2008).
Flexibility in the site of exon junction complex deposition revealed by functional group and RNA secondary structure alterations in the splicing substrate.
  RNA, 14, 2657-2670.  
19088201 F.Liu, A.Putnam, and E.Jankowsky (2008).
ATP hydrolysis is required for DEAD-box protein recycling but not for duplex unwinding.
  Proc Natl Acad Sci U S A, 105, 20209-20214.  
18066079 H.Chamieh, L.Ballut, F.Bonneau, and H.Le Hir (2008).
NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity.
  Nat Struct Mol Biol, 15, 85-93.  
18164611 H.Le Hir, and G.R.Andersen (2008).
Structural insights into the exon junction complex.
  Curr Opin Struct Biol, 18, 112-119.  
18332124 J.Banroques, O.Cordin, M.Doère, P.Linder, and N.K.Tanner (2008).
A conserved phenylalanine of motif IV in superfamily 2 helicases is required for cooperative, ATP-dependent binding of RNA substrates in DEAD-box proteins.
  Mol Cell Biol, 28, 3359-3371.  
18480465 J.Feng, M.A.Lawson, and P.Melamed (2008).
A proteomic comparison of immature and mature mouse gonadotrophs reveals novel differentially expressed nuclear proteins that regulate gonadotropin gene transcription and RNA splicing.
  Biol Reprod, 79, 546-561.  
18270573 L.Lindqvist, M.Oberer, M.Reibarkh, R.Cencic, M.E.Bordeleau, E.Vogt, A.Marintchev, J.Tanaka, F.Fagotto, M.Altmann, G.Wagner, and J.Pelletier (2008).
Selective pharmacological targeting of a DEAD box RNA helicase.
  PLoS ONE, 3, e1583.  
18782831 M.H.Linden, R.K.Hartmann, and D.Klostermeier (2008).
The putative RNase P motif in the DEAD box helicase Hera is dispensable for efficient interaction with RNA and helicase activity.
  Nucleic Acids Res, 36, 5800-5811.  
18550358 M.S.Jurica (2008).
Detailed close-ups and the big picture of spliceosomes.
  Curr Opin Struct Biol, 18, 315-320.  
18719248 N.Rozovsky, A.C.Butterworth, and M.J.Moore (2008).
Interactions between eIF4AI and its accessory factors eIF4B and eIF4H.
  RNA, 14, 2136-2148.  
18606994 P.Schütz, M.Bumann, A.E.Oberholzer, C.Bieniossek, H.Trachsel, M.Altmann, and U.Baumann (2008).
Crystal structure of the yeast eIF4A-eIF4G complex: an RNA-helicase controlled by protein-protein interactions.
  Proc Natl Acad Sci U S A, 105, 9564-9569.
PDB codes: 2vso 2vsx
18267970 R.Lewis, H.Dürr, K.P.Hopfner, and J.Michaelis (2008).
Conformational changes of a Swi2/Snf2 ATPase during its mechano-chemical cycle.
  Nucleic Acids Res, 36, 1881-1890.  
19088196 Y.Chen, J.P.Potratz, P.Tijerina, M.Del Campo, A.M.Lambowitz, and R.Russell (2008).
DEAD-box proteins can completely separate an RNA duplex using a single ATP.
  Proc Natl Acad Sci U S A, 105, 20203-20208.  
17229151 A.R.Karow, B.Theissen, and D.Klostermeier (2007).
Authentic interdomain communication in an RNA helicase reconstituted by expressed protein ligation of two helicase domains.
  FEBS J, 274, 463-473.  
17473849 B.M.Lunde, C.Moore, and G.Varani (2007).
RNA-binding proteins: modular design for efficient function.
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17375189 C.G.Noble, and H.Song (2007).
MLN51 stimulates the RNA-helicase activity of eIF4AIII.
  PLoS ONE, 2, e303.  
17459736 C.Giorgi, and M.J.Moore (2007).
The nuclear nurture and cytoplasmic nature of localized mRNPs.
  Semin Cell Dev Biol, 18, 186-193.  
17628520 D.H.Parma, P.E.Bennett, and R.E.Boswell (2007).
Mago Nashi and Tsunagi/Y14, respectively, regulate Drosophila germline stem cell differentiation and oocyte specification.
  Dev Biol, 308, 507-519.  
17574830 E.Jankowsky, and M.E.Fairman (2007).
RNA helicases--one fold for many functions.
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17679086 F.Bleichert, and S.J.Baserga (2007).
The long unwinding road of RNA helicases.
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17558417 K.Büttner, S.Nehring, and K.P.Hopfner (2007).
Structural basis for DNA duplex separation by a superfamily-2 helicase.
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PDB codes: 2p6r 2p6u
17157498 K.P.Hopfner, and J.Michaelis (2007).
Mechanisms of nucleic acid translocases: lessons from structural biology and single-molecule biophysics.
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17868112 L.S.Salinas, E.Maldonado, M.Macías-Silva, T.K.Blackwell, and R.E.Navarro (2007).
The DEAD box RNA helicase VBH-1 is required for germ cell function in C. elegans.
  Genesis, 45, 533-546.  
17586820 M.H.Viegas, N.H.Gehring, S.Breit, M.W.Hentze, and A.E.Kulozik (2007).
The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway.
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17964264 Q.Yang, M.Del Campo, A.M.Lambowitz, and E.Jankowsky (2007).
DEAD-box proteins unwind duplexes by local strand separation.
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17656723 S.Myong, M.M.Bruno, A.M.Pyle, and T.Ha (2007).
Spring-loaded mechanism of DNA unwinding by hepatitis C virus NS3 helicase.
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17584618 W.K.Low, Y.Dang, S.Bhat, D.Romo, and J.O.Liu (2007).
Substrate-dependent targeting of eukaryotic translation initiation factor 4A by pateamine A: negation of domain-linker regulation of activity.
  Chem Biol, 14, 715-727.  
17606899 Z.Zhang, and A.R.Krainer (2007).
Splicing remodels messenger ribonucleoprotein architecture via eIF4A3-dependent and -independent recruitment of exon junction complex components.
  Proc Natl Acad Sci U S A, 104, 11574-11579.  
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.