spacer
spacer

PDBsum entry 1rk8

Go to PDB code: 
protein metals Protein-protein interface(s) links
Translation PDB id
1rk8
Jmol
Contents
Protein chains
87 a.a. *
127 a.a. *
33 a.a. *
Metals
_CA ×3
Waters ×142
* Residue conservation analysis
PDB id:
1rk8
Name: Translation
Title: Structure of the cytosolic protein pym bound to the mago- y14 core of the exon junction complex
Structure: Cg8781-pa protein. Chain: a. Fragment: rbd domain. Synonym: cg8781-pa. Engineered: yes. Mago nashi protein. Chain: b. Fragment: full-length. Synonym: cg9401-pa.
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: tsu. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: mago,mgn,cg9401. Gene: wibg,pym,cg30176/cg10330.
Biol. unit: Trimer (from PQS)
Resolution:
1.90Å     R-factor:   0.235     R-free:   0.249
Authors: F.Bono,J.Ebert,T.Guettler,E.Izaurralde,E.Conti
Key ref:
F.Bono et al. (2004). Molecular insights into the interaction of PYM with the Mago-Y14 core of the exon junction complex. EMBO Rep, 5, 304-310. PubMed id: 14968132 DOI: 10.1038/sj.embor.7400091
Date:
21-Nov-03     Release date:   13-Apr-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9V535  (RBM8A_DROME) -  RNA-binding protein 8A
Seq:
Struc:
165 a.a.
87 a.a.
Protein chain
Pfam   ArchSchema ?
P49028  (MGN_DROME) -  Protein mago nashi
Seq:
Struc:
147 a.a.
127 a.a.
Protein chain
Pfam   ArchSchema ?
P82804  (WIBG_DROME) -  Partner of Y14 and mago
Seq:
Struc:
207 a.a.
33 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     catalytic step 2 spliceosome   6 terms 
  Biological process     multicellular organismal development   25 terms 
  Biochemical function     nucleotide binding     6 terms  

 

 
DOI no: 10.1038/sj.embor.7400091 EMBO Rep 5:304-310 (2004)
PubMed id: 14968132  
 
 
Molecular insights into the interaction of PYM with the Mago-Y14 core of the exon junction complex.
F.Bono, J.Ebert, L.Unterholzner, T.Güttler, E.Izaurralde, E.Conti.
 
  ABSTRACT  
 
The exon junction complex (EJC) is deposited on mRNAs as a consequence of splicing and influences postsplicing mRNA metabolism. The Mago-Y14 heterodimer is a core component of the EJC. Recently, the protein PYM has been identified as an interacting partner of Mago-Y14. Here we show that PYM is a cytoplasmic RNA-binding protein that is excluded from the nucleus by Crm1. PYM interacts directly with Mago-Y14 by means of its N-terminal domain. The crystal structure of the Drosophila ternary complex at 1.9 A resolution reveals that PYM binds Mago and Y14 simultaneously, capping their heterodimerization interface at conserved surface residues. Formation of this ternary complex is also observed with the human proteins. Mago residues involved in the interaction with PYM have been implicated in nonsense-mediated mRNA decay (NMD). Consistently, human PYM is active in NMD tethering assays. Together, these data suggest a role for PYM in NMD.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 PYM binds Mago -Y14 with extensive interactions. (A) Schematic view of the PYM -Mago -Y14 complex (left panel) and schematic diagram highlighting the key residues involved in the interaction (right panel). Positively charged residues of PYM interact with negatively charged residues of Mago helices 1 and 2. In addition, PYM interacts with the 2 - 3 loop of Y14 by means of hydrophobic contacts. Colours are as in Fig 2. Hydrogen bonds are shown with dotted lines. (B) Stereo representation of the structure and of the interacting residues in a similar orientation as in Figs 2A,3A.
Figure 4.
Figure 4 The PYM -Mago -Y14 complex is conserved across species. (A) The interaction surfaces of D. melanogaster PYM and the Mago -Y14 heterodimer have been opened up relative to the view in Fig 2A. The two surfaces are coloured according to sequence conservation, ranging from orange for conserved residues to white for variable residues. On the right, the atomic model of PYM is shown bound to the surface of Mago -Y14. (B) Lysates prepared from E. coli expressing untagged H. sapiens (Hs) PYM were incubated with glutathione agarose beads coated with GST, GST -Hs Y14, GST -Hs Mago or GST -Hs Y14 -Mago dimers.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO Rep (2004, 5, 304-310) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20711187 C.D.Cukier, D.Hollingworth, S.R.Martin, G.Kelly, I.Díaz-Moreno, and A.Ramos (2010).
Molecular basis of FIR-mediated c-myc transcriptional control.
  Nat Struct Mol Biol, 17, 1058-1064.  
20479275 G.Buchwald, J.Ebert, C.Basquin, J.Sauliere, U.Jayachandran, F.Bono, H.Le Hir, and E.Conti (2010).
Insights into the recruitment of the NMD machinery from the crystal structure of a core EJC-UPF3b complex.
  Proc Natl Acad Sci U S A, 107, 10050-10055.
PDB code: 2xb2
20436455 J.R.Boyne, B.R.Jackson, A.Taylor, S.A.Macnab, and A.Whitehouse (2010).
Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with PYM to enhance translation of viral intronless mRNAs.
  EMBO J, 29, 1851-1864.  
19410547 N.H.Gehring, S.Lamprinaki, A.E.Kulozik, and M.W.Hentze (2009).
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.  
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.  
18716674 S.Shazman, and Y.Mandel-Gutfreund (2008).
Classifying RNA-binding proteins based on electrostatic properties.
  PLoS Comput Biol, 4, e1000146.  
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.  
17459736 C.Giorgi, and M.J.Moore (2007).
The nuclear nurture and cytoplasmic nature of localized mRNPs.
  Semin Cell Dev Biol, 18, 186-193.  
18026120 M.D.Diem, C.C.Chan, I.Younis, and G.Dreyfuss (2007).
PYM binds the cytoplasmic exon-junction complex and ribosomes to enhance translation of spliced mRNAs.
  Nat Struct Mol Biol, 14, 1173-1179.  
16953428 N.I.Park, and D.G.Muench (2007).
Biochemical and cellular characterization of the plant ortholog of PYM, a protein that interacts with the exon junction complex core proteins Mago and Y14.
  Planta, 225, 625-639.  
17352659 Y.F.Chang, J.S.Imam, and M.F.Wilkinson (2007).
The nonsense-mediated decay RNA surveillance pathway.
  Annu Rev Biochem, 76, 51-74.  
16931718 C.B.Andersen, L.Ballut, J.S.Johansen, H.Chamieh, K.H.Nielsen, C.L.Oliveira, J.S.Pedersen, B.Séraphin, H.Le Hir, and G.R.Andersen (2006).
Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA.
  Science, 313, 1968-1972.
PDB codes: 2hxy 2hyi
17001100 C.Romier, M.Ben Jelloul, S.Albeck, G.Buchwald, D.Busso, P.H.Celie, E.Christodoulou, V.De Marco, S.van Gerwen, P.Knipscheer, J.H.Lebbink, V.Notenboom, A.Poterszman, N.Rochel, S.X.Cohen, T.Unger, J.L.Sussman, D.Moras, T.K.Sixma, and A.Perrakis (2006).
Co-expression of protein complexes in prokaryotic and eukaryotic hosts: experimental procedures, database tracking and case studies.
  Acta Crystallogr D Biol Crystallogr, 62, 1232-1242.  
16923391 F.Bono, J.Ebert, E.Lorentzen, and E.Conti (2006).
The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA.
  Cell, 126, 713-725.
PDB codes: 2j0q 2j0s 2j0u
16601204 J.B.Kunz, G.Neu-Yilik, M.W.Hentze, A.E.Kulozik, and N.H.Gehring (2006).
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation.
  RNA, 12, 1015-1022.  
15853797 C.Maris, C.Dominguez, and F.H.Allain (2005).
The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression.
  FEBS J, 272, 2118-2131.  
15901503 E.Conti, and E.Izaurralde (2005).
Nonsense-mediated mRNA decay: molecular insights and mechanistic variations across species.
  Curr Opin Cell Biol, 17, 316-325.  
15901502 F.Lejeune, and L.E.Maquat (2005).
Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells.
  Curr Opin Cell Biol, 17, 309-315.  
16100109 I.a.W.Hsu, M.Hsu, C.Li, T.W.Chuang, R.I.Lin, and W.Y.Tarn (2005).
Phosphorylation of Y14 modulates its interaction with proteins involved in mRNA metabolism and influences its methylation.
  J Biol Chem, 280, 34507-34512.  
16209946 N.H.Gehring, J.B.Kunz, G.Neu-Yilik, S.Breit, M.H.Viegas, M.W.Hentze, and A.E.Kulozik (2005).
Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements.
  Mol Cell, 20, 65-75.  
15680326 Y.K.Kim, L.Furic, L.Desgroseillers, and L.E.Maquat (2005).
Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay.
  Cell, 120, 195-208.  
15284851 J.A.Holbrook, G.Neu-Yilik, M.W.Hentze, and A.E.Kulozik (2004).
Nonsense-mediated decay approaches the clinic.
  Nat Genet, 36, 801-808.  
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.