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RNA-binding protein PDB id
1uw4
Jmol
Contents
Protein chains
91 a.a. *
248 a.a. *
Ligands
BME ×2
Waters ×314
* Residue conservation analysis
PDB id:
1uw4
Name: RNA-binding protein
Title: The structural basis of the interaction between nonsense mediated decay factors upf2 and upf3
Structure: Regulator of nonsense transcripts 2. Chain: b, d. Fragment: mif4g domain, residues 768-1015. Synonym: upf2. Engineered: yes. Upf3x. Chain: a, c. Fragment: rrm domain, residues 50-140. Synonym: RNA processing protein, upf3b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: hela-cell. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
Resolution:
1.95Å     R-factor:   0.205     R-free:   0.227
Authors: J.Kadlec,E.Izaurralde,S.Cusack
Key ref:
J.Kadlec et al. (2004). The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3. Nat Struct Mol Biol, 11, 330-337. PubMed id: 15004547 DOI: 10.1038/nsmb741
Date:
29-Jan-04     Release date:   11-Mar-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9BZI7  (REN3B_HUMAN) -  Regulator of nonsense transcripts 3B
Seq:
Struc: 		483 a.a.
91 a.a.
Protein chains
Pfam   ArchSchema ?
Q9HAU5  (RENT2_HUMAN) -  Regulator of nonsense transcripts 2
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1272 a.a.
248 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     RNA metabolic process   1 term 
  Biochemical function     binding     3 terms  

 

 
DOI no: 10.1038/nsmb741 Nat Struct Mol Biol 11:330-337 (2004)
PubMed id: 15004547  
 
 
The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3.
J.Kadlec, E.Izaurralde, S.Cusack.
 
  ABSTRACT  
 
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism by which eukaryotic cells detect and degrade transcripts containing premature termination codons. Three 'up-frameshift' proteins, UPF1, UPF2 and UPF3, are essential for this process in organisms ranging from yeast to human. We present a crystal structure at a resolution of 1.95 A of the complex between the interacting domains of human UPF2 and UPF3b, which are, respectively, a MIF4G (middle portion of eIF4G) domain and an RNP domain (ribonucleoprotein-type RNA-binding domain). The protein-protein interface is mediated by highly conserved charged residues in UPF2 and UPF3b and involves the beta-sheet surface of the UPF3b RNP domain, which is generally used by these domains to bind nucleic acids. We show that the UPF3b RNP does not bind RNA, whereas the UPF2 construct and the complex do. Our results advance understanding of the molecular mechanisms underlying the NMD quality control process.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Crystal structure of the complex between UPF2 and UPF3b. (a) UPF3b(42 -143) RNP domain (blue) interacts with helix 5 of UPF2(761 -1054) (red) through its -sheet. Secondary structures of both proteins are labeled. UPF2 MIF4G domain comprises helices 1 -10. (b) A representative part of the 2F[0]- F[c] electron density map contoured at 2.2 , corresponding to the principal UPF2-UPF3b interaction region (UPF2 residues, orange; UPF3b residues, yellow). (c) Schematic representation of principal interactions between UPF2 helix 5 (residues, orange; helix, red) and UPF3b -sheet (residues, yellow; -strands, blue) as well as Lys52 interactions with the UPF3b C-terminal loop (residues 134 -140). These figures and ribbon diagrams in Figure 3 were generated with MolScript46 and BobScript47. 		Figure 3.
Figure 3. Structure and surface characteristics of the UPF2 -UPF3b complex and a comparison with the Y14 -Mago complex. (a) Superposition of human UPF2(770 -983) (red) and CBP80(26 -243) (yellow) MIF4G domains. Secondary structures are labeled according to UPF2. (b) Surface representation of the human UPF2(761 -1054) -UPF3b(42 -143) complex. Conserved surface residues (S. pombe sequence excluded) are represented from white to green according to the scale. All the labeled residues belong to UPF2. The complex is rotated -30° around the vertical axis relative to a. The figure was generated using GRASP48. (c) Ribbon representation of the UPF2(761 -1054) -UPF3b(42 -143) complex in the same orientation as in b, showing the conserved surface residues of UPF2 labeled in b. (d,e) Comparison of the UPF2 -UPF3b and Y14 -Mago complexes. (d) UPF3b -sheet (blue) interacting with UPF2 helix 5 and 6 (red). Helix 5 is orientated across the -sheet. (e) The Mago helices 1 and 3 (yellow) bind parallel to the flat Y14 -sheet (green)6. The figure is based on the superposition of Y14 and UPF3b RNP domains with a Dali Z-score of 8.8.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2004, 11, 330-337) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21419344 S.Chakrabarti, U.Jayachandran, F.Bonneau, F.Fiorini, C.Basquin, S.Domcke, H.Le Hir, and E.Conti (2011).
Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2.
  Mol Cell, 41, 693-703.
PDB codes: 2xzl 2xzo 2xzp
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.  
19920119 C.M.Gould, F.Diella, A.Via, P.Puntervoll, C.Gemünd, S.Chabanis-Davidson, S.Michael, A.Sayadi, J.C.Bryne, C.Chica, M.Seiler, N.E.Davey, N.Haslam, R.J.Weatheritt, A.Budd, T.Hughes, J.Pas, L.Rychlewski, G.Travé, R.Aasland, M.Helmer-Citterich, R.Linding, and T.J.Gibson (2010).
ELM: the status of the 2010 eukaryotic linear motif resource.
  Nucleic Acids Res, 38, D167-D180.  
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
20795950 M.Bhuvanagiri, A.M.Schlitter, M.W.Hentze, and A.E.Kulozik (2010).
NMD: RNA biology meets human genetic medicine.
  Biochem J, 430, 365-377.  
19859661 P.Nicholson, H.Yepiskoposyan, S.Metze, R.Zamudio Orozco, N.Kleinschmidt, and O.Mühlemann (2010).
Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors.
  Cell Mol Life Sci, 67, 677-700.  
19295135 A.Eulalio, F.Tritschler, R.Büttner, O.Weichenrieder, E.Izaurralde, and V.Truffault (2009).
The RRM domain in GW182 proteins contributes to miRNA-mediated gene silencing.
  Nucleic Acids Res, 37, 2974-2983.
PDB code: 2wbr
19852836 A.Via, C.M.Gould, C.Gemünd, T.J.Gibson, and M.Helmer-Citterich (2009).
A structure filter for the Eukaryotic Linear Motif Resource.
  BMC Bioinformatics, 10, 351.  
19523901 J.H.Lee, E.S.Rangarajan, S.D.Yogesha, and T.Izard (2009).
Raver1 interactions with vinculin and RNA suggest a feed-forward pathway in directing mRNA to focal adhesions.
  Structure, 17, 833-842.
PDB codes: 3h2u 3h2v
19556969 M.Clerici, A.Mourão, I.Gutsche, N.H.Gehring, M.W.Hentze, A.Kulozik, J.Kadlec, M.Sattler, and S.Cusack (2009).
Unusual bipartite mode of interaction between the nonsense-mediated decay factors, UPF1 and UPF2.
  EMBO J, 28, 2293-2306.
PDB codes: 2wjv 2wjy
19435450 M.D.Bashyam (2009).
Nonsense-mediated decay: linking a basic cellular process to human disease.
  Expert Rev Mol Diagn, 9, 299-303.  
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.  
18615715 S.Ohnishi, K.Pääkkönen, S.Koshiba, N.Tochio, M.Sato, N.Kobayashi, T.Harada, S.Watanabe, Y.Muto, P.Güntert, A.Tanaka, T.Kigawa, and S.Yokoyama (2009).
Solution structure of the GUCT domain from human RNA helicase II/Gu beta reveals the RRM fold, but implausible RNA interactions.
  Proteins, 74, 133-144.
PDB code: 2e29
19503078 W.K.Chan, A.D.Bhalla, H.Le Hir, L.S.Nguyen, L.Huang, J.Gécz, and M.F.Wilkinson (2009).
A UPF3-mediated regulatory switch that maintains RNA surveillance.
  Nat Struct Mol Biol, 16, 747-753.  
18201561 A.O.Kumar, M.C.Swenson, M.M.Benning, and C.L.Kielkopf (2008).
Structure of the central RNA recognition motif of human TIA-1 at 1.95A resolution.
  Biochem Biophys Res Commun, 367, 813-819.
PDB code: 3bs9
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.  
18076038 K.Kuwasako, N.Dohmae, M.Inoue, M.Shirouzu, S.Taguchi, P.Güntert, B.Séraphin, Y.Muto, and S.Yokoyama (2008).
Complex assembly mechanism and an RNA-binding mode of the human p14-SF3b155 spliceosomal protein complex identified by NMR solution structure and functional analyses.
  Proteins, 71, 1617-1636.  
18524595 L.Stalder, and O.Mühlemann (2008).
The meaning of nonsense.
  Trends Cell Biol, 18, 315-321.  
17229474 D.M.Lehmann, C.A.Galloway, C.MacElrevey, M.P.Sowden, J.E.Wedekind, and H.C.Smith (2007).
Functional characterization of APOBEC-1 complementation factor phosphorylation sites.
  Biochim Biophys Acta, 1773, 408-418.  
17190833 L.ElAntak, A.G.Tzakos, N.Locker, and P.J.Lukavsky (2007).
Structure of eIF3b RNA recognition motif and its interaction with eIF3j: structural insights into the recruitment of eIF3b to the 40 S ribosomal subunit.
  J Biol Chem, 282, 8165-8174.
PDB code: 2nlw
17562857 L.Johns, A.Grimson, S.L.Kuchma, C.L.Newman, and P.Anderson (2007).
Caenorhabditis elegans SMG-2 selectively marks mRNAs containing premature translation termination codons.
  Mol Cell Biol, 27, 5630-5638.  
17060447 N.LaRonde-LeBlanc, A.N.Santhanam, A.R.Baker, A.Wlodawer, and N.H.Colburn (2007).
Structural basis for inhibition of translation by the tumor suppressor Pdcd4.
  Mol Cell Biol, 27, 147-156.
PDB codes: 2iol 2ion 2ios 2nsz
17704778 P.S.Tarpey, F.L.Raymond, L.S.Nguyen, J.Rodriguez, A.Hackett, L.Vandeleur, R.Smith, C.Shoubridge, S.Edkins, C.Stevens, S.O'Meara, C.Tofts, S.Barthorpe, G.Buck, J.Cole, K.Halliday, K.Hills, D.Jones, T.Mironenko, J.Perry, J.Varian, S.West, S.Widaa, J.Teague, E.Dicks, A.Butler, A.Menzies, D.Richardson, A.Jenkinson, R.Shepherd, K.Raine, J.Moon, Y.Luo, J.Parnau, S.S.Bhat, A.Gardner, M.Corbett, D.Brooks, P.Thomas, E.Parkinson-Lawrence, M.E.Porteous, J.P.Warner, T.Sanderson, P.Pearson, R.J.Simensen, C.Skinner, G.Hoganson, D.Superneau, R.Wooster, M.Bobrow, G.Turner, R.E.Stevenson, C.E.Schwartz, P.A.Futreal, A.K.Srivastava, M.R.Stratton, and J.Gécz (2007).
Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation.
  Nat Genet, 39, 1127-1133.  
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.  
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.  
16452507 I.Kashima, A.Yamashita, N.Izumi, N.Kataoka, R.Morishita, S.Hoshino, M.Ohno, G.Dreyfuss, and S.Ohno (2006).
Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay.
  Genes Dev, 20, 355-367.  
16963627 I.Y.Morozov, S.Negrete-Urtasun, J.Tilburn, C.A.Jansen, M.X.Caddick, and H.N.Arst (2006).
Nonsense-mediated mRNA decay mutation in Aspergillus nidulans.
  Eukaryot Cell, 5, 1838-1846.  
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.  
16931876 J.Kadlec, D.Guilligay, R.B.Ravelli, and S.Cusack (2006).
Crystal structure of the UPF2-interacting domain of nonsense-mediated mRNA decay factor UPF1.
  RNA, 12, 1817-1824.
PDB code: 2iyk
16611983 W.Wang, I.J.Cajigas, S.W.Peltz, M.F.Wilkinson, and C.I.González (2006).
Role for Upf2p phosphorylation in Saccharomyces cerevisiae nonsense-mediated mRNA decay.
  Mol Cell Biol, 26, 3390-3400.  
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.  
15933735 M.B.Fasken, and A.H.Corbett (2005).
Process or perish: quality control in mRNA biogenesis.
  Nat Struct Mol Biol, 12, 482-488.  
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.  
16186820 N.Hosoda, Y.K.Kim, F.Lejeune, and L.E.Maquat (2005).
CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells.
  Nat Struct Mol Biol, 12, 893-901.  
16109371 O.Hantschel, S.Wiesner, T.Güttler, C.D.Mackereth, L.L.Rix, Z.Mikes, J.Dehne, D.Görlich, M.Sattler, and G.Superti-Furga (2005).
Structural basis for the cytoskeletal association of Bcr-Abl/c-Abl.
  Mol Cell, 19, 461-473.
PDB code: 1zzp
16077728 R.Singh, and J.Valcárcel (2005).
Building specificity with nonspecific RNA-binding proteins.
  Nat Struct Mol Biol, 12, 645-653.  
15231733 C.L.Kielkopf, S.Lücke, and M.R.Green (2004).
U2AF homology motifs: protein recognition in the RRM world.
  Genes Dev, 18, 1513-1526.  
15547136 N.Kuperwasser, S.Brogna, K.Dower, and M.Rosbash (2004).
Nonsense-mediated decay does not occur within the yeast nucleus.
  RNA, 10, 1907-1915.  
15299008 Y.Iko, T.S.Kodama, N.Kasai, T.Oyama, E.H.Morita, T.Muto, M.Okumura, R.Fujii, T.Takumi, S.Tate, and K.Morikawa (2004).
Domain architectures and characterization of an RNA-binding protein, TLS.
  J Biol Chem, 279, 44834-44840.  
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.