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PDBsum entry 1fje

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protein dna_rna links
Structural protein/RNA PDB id
1fje
Jmol
Contents
Protein chain
175 a.a. *
DNA/RNA
* Residue conservation analysis
PDB id:
1fje
Name: Structural protein/RNA
Title: Solution structure of nucleolin rbd12 in complex with snre RNA
Structure: Snre RNA. Chain: a. Engineered: yes. Other_details: in vitro selected RNA. Nucleolin rbd12. Chain: b. Fragment: two n-terminal rbd domains. Synonym: protein c23. Engineered: yes
Source: Synthetic: yes. Other_details: in vitro transcription by t7 RNA polymerase. Mesocricetus auratus. Golden hamster. Organism_taxid: 10036. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 19 models
Authors: F.H.T.Allain,P.Bouvet,T.Dieckmann,J.Feigon
Key ref:
F.H.Allain et al. (2000). Molecular basis of sequence-specific recognition of pre-ribosomal RNA by nucleolin. EMBO J, 19, 6870-6881. PubMed id: 11118222 DOI: 10.1093/emboj/19.24.6870
Date:
08-Aug-00     Release date:   03-Jan-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08199  (NUCL_MESAU) -  Nucleolin
Seq:
Struc:
 
Seq:
Struc:
714 a.a.
175 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     nucleotide binding     2 terms  

 

 
DOI no: 10.1093/emboj/19.24.6870 EMBO J 19:6870-6881 (2000)
PubMed id: 11118222  
 
 
Molecular basis of sequence-specific recognition of pre-ribosomal RNA by nucleolin.
F.H.Allain, P.Bouvet, T.Dieckmann, J.Feigon.
 
  ABSTRACT  
 
The structure of the 28 kDa complex of the first two RNA binding domains (RBDs) of nucleolin (RBD12) with an RNA stem-loop that includes the nucleolin recognition element UCCCGA in the loop was determined by NMR spectroscopy. The structure of nucleolin RBD12 with the nucleolin recognition element (NRE) reveals that the two RBDs bind on opposite sides of the RNA loop, forming a molecular clamp that brings the 5' and 3' ends of the recognition sequence close together and stabilizing the stem-loop. The specific interactions observed in the structure explain the sequence specificity for the NRE sequence. Binding studies of mutant proteins and analysis of conserved residues support the proposed interactions. The mode of interaction of the protein with the RNA and the location of the putative NRE sites suggest that nucleolin may function as an RNA chaperone to prevent improper folding of the nascent pre-rRNA.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 Overall description of the complex. The lowest energy structure is shown. (A) Stick (RNA) and ribbon (protein) representation of the complex showing how the RNA loop is 'sandwiched' between the two RBDs. RBD1 is located in the major groove side of the RNA and contacts C12, G13 and the loop E motif. RBD2 is located on the minor groove side and contacts U9 and C10. The linker is mostly located in the minor groove side on the RNA. The amino acid side chains from RBD1 V27, K31 ( -helix 1) and T52, R54 ( 2– 3 loop), which contact the stem, as well as the inserting residues F56 and K94, are shown in blue. (B) Surface representation of the RNA and protein complex. The view is the same as in (A). (C) View of the complex showing that the two RBDs interact via two salt bridges (K89–E125 and K55–D132). Asp and Glu are shown in red and Lys and Arg in blue. The major groove face of the binding site is shown. (D) GRASP (Nicholls et al., 1991) representation of the complex with positively charged residues in blue and negatively charged residues in red. The color scheme is the same as Figure 2, except for the GRASP representation.
Figure 8.
Figure 8 Proposed model of the RNA chaperone activity of nucleolin for proper folding of the 5' ETS region between nucleotides 1671 and 3549 of human 47S pre-rRNA. A schematic representation of the predicted secondary structure of this region in the mature pre-rRNA based on phylogeny (Renalier et al., 1989) and electron microscopy (Wellauer et al., 1974; Schibler et al., 1975) studies is shown on the right. The putative NRE binding sites in this sequence are indicated by black rectangles. They are all found in double-stranded regions of the mature pre-rRNA, so nucleolin (indicated by the black oval ring) is not expected to be bound. On the left side of the figure are shown schematically two alternate structures that the RNA can adopt with (top) or without (bottom) nucleolin. Without nucleolin, the RNA can be kinetically trapped in alternative stable structures, which have to unfold to form the mature pre-rRNA, with the result that formation of the mature pre-rRNA will be slow. The bound nucleolin promotes and/or stabilizes stem–loops at the NRE consensus sites, preventing the formation of alternative stable helices, and then dissociates to allow the final structure to form.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 6870-6881) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21241883 C.Dominguez, M.Schubert, O.Duss, S.Ravindranathan, and F.H.Allain (2011).
Structure determination and dynamics of protein-RNA complexes by NMR spectroscopy.
  Prog Nucl Magn Reson Spectrosc, 58, 1.  
21419778 D.Anunciado, A.Dhar, M.Gruebele, and A.M.Baranger (2011).
Multistep kinetics of the U1A-SL2 RNA complex dissociation.
  J Mol Biol, 408, 896-908.  
  21501365 H.Zakaryan, and T.Stamminger (2011).
Nuclear remodelling during viral infections.
  Cell Microbiol, 13, 806-813.  
20479262 Q.Yang, G.M.Gilmartin, and S.Doublié (2010).
Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing.
  Proc Natl Acad Sci U S A, 107, 10062-10067.
PDB codes: 3mdg 3mdi
20376532 S.Arumugam, M.C.Miller, J.Maliekal, P.J.Bates, J.O.Trent, and A.N.Lane (2010).
Solution structure of the RBD1,2 domains from human nucleolin.
  J Biomol NMR, 47, 79-83.
PDB code: 2krr
19581307 V.González, K.Guo, L.Hurley, and D.Sun (2009).
Identification and characterization of nucleolin as a c-myc G-quadruplex-binding protein.
  J Biol Chem, 284, 23622-23635.  
19170763 Y.Hirano, K.Ishii, M.Kumeta, K.Furukawa, K.Takeyasu, and T.Horigome (2009).
Proteomic and targeted analytical identification of BXDC1 and EBNA1BP2 as dynamic scaffold proteins in the nucleolus.
  Genes Cells, 14, 155-166.  
18515081 A.Cléry, M.Blatter, and F.H.Allain (2008).
RNA recognition motifs: boring? Not quite.
  Curr Opin Struct Biol, 18, 290-298.  
18293956 D.Anunciado, M.Agumeh, B.L.Kormos, D.L.Beveridge, J.L.Knee, and A.M.Baranger (2008).
Characterization of the dynamics of an essential helix in the U1A protein by time-resolved fluorescence measurements.
  J Phys Chem B, 112, 6122-6130.  
19079550 K.N.Rao, S.K.Burley, and S.Swaminathan (2008).
UPF201 archaeal specific family members reveal structural similarity to RNA-binding proteins but low likelihood for RNA-binding function.
  PLoS ONE, 3, e3903.
PDB codes: 2nrq 2nwu 2ogk 2pzz
18160411 N.J.Reiter, L.J.Maher, and S.E.Butcher (2008).
DNA mimicry by a high-affinity anti-NF-kappaB RNA aptamer.
  Nucleic Acids Res, 36, 1227-1236.
PDB code: 2jwv
17997079 S.H.Fatemi, T.D.Folsom, T.J.Reutiman, and R.W.Sidwell (2008).
Viral regulation of aquaporin 4, connexin 43, microcephalin and nucleolin.
  Schizophr Res, 98, 163-177.  
17654514 T.Sweet, W.Yen, K.Khalili, and S.Amini (2008).
Evidence for involvement of NFBP in processing of ribosomal RNA.
  J Cell Physiol, 214, 381-388.  
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.  
17108323 F.Pontvianne, I.Matía, J.Douet, S.Tourmente, F.J.Medina, M.Echeverria, and J.Sáez-Vásquez (2007).
Characterization of AtNUC-L1 reveals a central role of nucleolin in nucleolus organization and silencing of AtNUC-L2 gene in Arabidopsis.
  Mol Biol Cell, 18, 369-379.  
17692122 I.Ugrinova, K.Monier, C.Ivaldi, M.Thiry, S.Storck, F.Mongelard, and P.Bouvet (2007).
Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication.
  BMC Mol Biol, 8, 66.  
16819967 B.K.Dove, J.H.You, M.L.Reed, S.R.Emmett, G.Brooks, and J.A.Hiscox (2006).
Changes in nucleolar morphology and proteins during infection with the coronavirus infectious bronchitis virus.
  Cell Microbiol, 8, 1147-1157.  
16431980 C.Clerte, and K.B.Hall (2006).
Characterization of multimeric complexes formed by the human PTB1 protein on RNA.
  RNA, 12, 457-475.  
16362043 F.Vitali, A.Henning, F.C.Oberstrass, Y.Hargous, S.D.Auweter, M.Erat, and F.H.Allain (2006).
Structure of the two most C-terminal RNA recognition motifs of PTB using segmental isotope labeling.
  EMBO J, 25, 150-162.
PDB code: 2evz
16794580 J.M.Pérez-Cañadillas (2006).
Grabbing the message: structural basis of mRNA 3'UTR recognition by Hrp1.
  EMBO J, 25, 3167-3178.
PDB code: 2cjk
16432215 M.J.Schellenberg, R.A.Edwards, D.B.Ritchie, O.A.Kent, M.M.Golas, H.Stark, R.Lührmann, J.N.Glover, and A.M.MacMillan (2006).
Crystal structure of a core spliceosomal protein interface.
  Proc Natl Acad Sci U S A, 103, 1266-1271.
PDB codes: 2f9d 2f9j
16452301 R.J.Richards, C.A.Theimer, L.D.Finger, and J.Feigon (2006).
Structure of the Tetrahymena thermophila telomerase RNA helix II template boundary element.
  Nucleic Acids Res, 34, 816-825.
PDB codes: 2frl 2m22
16982642 S.D.Auweter, F.C.Oberstrass, and F.H.Allain (2006).
Sequence-specific binding of single-stranded RNA: is there a code for recognition?
  Nucleic Acids Res, 34, 4943-4959.  
16362037 S.D.Auweter, R.Fasan, L.Reymond, J.G.Underwood, D.L.Black, S.Pitsch, and F.H.Allain (2006).
Molecular basis of RNA recognition by the human alternative splicing factor Fox-1.
  EMBO J, 25, 163-173.
PDB code: 2err
16611943 S.Wang, Y.Hu, M.T.Overgaard, F.V.Karginov, O.C.Uhlenbeck, and D.B.McKay (2006).
The domain of the Bacillus subtilis DEAD-box helicase YxiN that is responsible for specific binding of 23S rRNA has an RNA recognition motif fold.
  RNA, 12, 959-967.
PDB code: 2g0c
16508016 Y.Jiang, X.S.Xu, and J.E.Russell (2006).
A nucleolin-binding 3' untranslated region element stabilizes beta-globin mRNA in vivo.
  Mol Cell Biol, 26, 2419-2429.  
16278830 Y.Zhao, B.L.Kormos, D.L.Beveridge, and A.M.Baranger (2006).
Molecular dynamics simulation studies of a protein-RNA complex with a selectively modified binding interface.
  Biopolymers, 81, 256-269.  
16122968 A.M.Bonvin, R.Boelens, and R.Kaptein (2005).
NMR analysis of protein interactions.
  Curr Opin Chem Biol, 9, 501-508.  
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.  
16179478 F.C.Oberstrass, S.D.Auweter, M.Erat, Y.Hargous, A.Henning, P.Wenter, L.Reymond, B.Amir-Ahmady, S.Pitsch, D.L.Black, and F.H.Allain (2005).
Structure of PTB bound to RNA: specific binding and implications for splicing regulation.
  Science, 309, 2054-2057.
PDB codes: 2ad9 2adb 2adc
15643449 R.Stefl, L.Skrisovska, and F.H.Allain (2005).
RNA sequence- and shape-dependent recognition by proteins in the ribonucleoprotein particle.
  EMBO Rep, 6, 33-38.  
15811912 S.S.Kwan, and D.A.Brow (2005).
The N- and C-terminal RNA recognition motifs of splicing factor Prp24 have distinct functions in U6 RNA binding.
  RNA, 11, 808-820.  
15853794 Y.Chen, and G.Varani (2005).
Protein families and RNA recognition.
  FEBS J, 272, 2088-2097.  
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.  
15282326 J.Sáez-Vasquez, D.Caparros-Ruiz, F.Barneche, and M.Echeverría (2004).
A plant snoRNP complex containing snoRNAs, fibrillarin, and nucleolin-like proteins is competent for both rRNA gene binding and pre-rRNA processing in vitro.
  Mol Cell Biol, 24, 7284-7297.  
15192703 N.Leulliot, S.Quevillon-Cheruel, M.Graille, H.van Tilbeurgh, T.C.Leeper, K.S.Godin, T.E.Edwards, S.T.Sigurdsson, N.Rozenkrants, R.J.Nagel, M.Ares, and G.Varani (2004).
A new alpha-helical extension promotes RNA binding by the dsRBD of Rnt1p RNAse III.
  EMBO J, 23, 2468-2477.
PDB codes: 1t4n 1t4o
15572691 R.V.Intine, M.Dundr, A.Vassilev, E.Schwartz, Y.Zhao, Y.Zhao, M.L.Depamphilis, and R.J.Maraia (2004).
Nonphosphorylated human La antigen interacts with nucleolin at nucleolar sites involved in rRNA biogenesis.
  Mol Cell Biol, 24, 10894-10904.  
15254186 S.Bose, M.Basu, and A.K.Banerjee (2004).
Role of nucleolin in human parainfluenza virus type 3 infection of human lung epithelial cells.
  J Virol, 78, 8146-8158.  
14679209 T.K.Sengupta, S.Bandyopadhyay, D.J.Fernandes, and E.K.Spicer (2004).
Identification of nucleolin as an AU-rich element binding protein involved in bcl-2 mRNA stabilization.
  J Biol Chem, 279, 10855-10863.  
12626338 D.L.Black (2003).
Mechanisms of alternative pre-messenger RNA splicing.
  Annu Rev Biochem, 72, 291-336.  
12809490 G.C.Pérez-Alvarado, M.Martínez-Yamout, M.M.Allen, R.Grosschedl, H.J.Dyson, and P.E.Wright (2003).
Structure of the nuclear factor ALY: insights into post-transcriptional regulatory and mRNA nuclear export processes.
  Biochemistry, 42, 7348-7357.
PDB code: 1no8
14602904 L.D.Finger, L.Trantirek, C.Johansson, and J.Feigon (2003).
Solution structures of stem-loop RNAs that bind to the two N-terminal RNA-binding domains of nucleolin.
  Nucleic Acids Res, 31, 6461-6472.
PDB codes: 1qwa 1qwb
12804115 S.K.Kim, and M.Srivastava (2003).
Stability of Nucleolin protein as the basis for the differential expression of Nucleolin mRNA and protein during serum starvation.
  DNA Cell Biol, 22, 171-178.  
12637556 U.Kühn, A.Nemeth, S.Meyer, and E.Wahle (2003).
The RNA binding domains of the nuclear poly(A)-binding protein.
  J Biol Chem, 278, 16916-16925.  
11773064 B.Roger, A.Moisand, F.Amalric, and P.Bouvet (2002).
Repression of RNA polymerase I transcription by nucleolin is independent of the RNA sequence that is transcribed.
  J Biol Chem, 277, 10209-10219.  
11967337 H.Chen, T.Wurm, P.Britton, G.Brooks, and J.A.Hiscox (2002).
Interaction of the coronavirus nucleoprotein with nucleolar antigens and the host cell.
  J Virol, 76, 5233-5250.  
11839490 H.J.Dyson, and P.E.Wright (2002).
Coupling of folding and binding for unstructured proteins.
  Curr Opin Struct Biol, 12, 54-60.  
12466552 J.B.Tuite, J.C.Shiels, and A.M.Baranger (2002).
Substitution of an essential adenine in the U1A-RNA complex with a non-polar isostere.
  Nucleic Acids Res, 30, 5269-5275.  
11917013 J.Vitali, J.Ding, J.Jiang, Y.Zhang, A.R.Krainer, and R.M.Xu (2002).
Correlated alternative side chain conformations in the RNA-recognition motif of heterogeneous nuclear ribonucleoprotein A1.
  Nucleic Acids Res, 30, 1531-1538.
PDB code: 1l3k
12093755 M.A.Schumacher, R.F.Pearson, T.Møller, P.Valentin-Hansen, and R.G.Brennan (2002).
Structures of the pleiotropic translational regulator Hfq and an Hfq-RNA complex: a bacterial Sm-like protein.
  EMBO J, 21, 3546-3556.
PDB codes: 1kq1 1kq2
12388766 P.Björk, G.Baurén, S.Jin, Y.G.Tong, T.R.Bürglin, U.Hellman, and L.Wieslander (2002).
A novel conserved RNA-binding domain protein, RBD-1, is essential for ribosome biogenesis.
  Mol Biol Cell, 13, 3683-3695.  
12082087 P.S.Katsamba, M.Bayramyan, I.S.Haworth, D.G.Myszka, and I.A.Laird-Offringa (2002).
Complex role of the beta 2-beta 3 loop in the interaction of U1A with U1 hairpin II RNA.
  J Biol Chem, 277, 33267-33274.  
11884397 S.B.Jin, J.Zhao, P.Bjork, K.Schmekel, P.O.Ljungdahl, and L.Wieslander (2002).
Mrd1p is required for processing of pre-rRNA and for maintenance of steady-state levels of 40 S ribosomal subunits in yeast.
  J Biol Chem, 277, 18431-18439.  
11788707 X.Yuan, N.Davydova, M.R.Conte, S.Curry, and S.Matthews (2002).
Chemical shift mapping of RNA interactions with the polypyrimidine tract binding protein.
  Nucleic Acids Res, 30, 456-462.  
11953318 Y.Yang, N.Declerck, X.Manival, S.Aymerich, and M.Kochoyan (2002).
Solution structure of the LicT-RNA antitermination complex: CAT clamping RAT.
  EMBO J, 21, 1987-1997.
PDB code: 1l1c
11514570 G.M.Wilson, K.Sutphen, M.Moutafis, S.Sinha, and G.Brewer (2001).
Structural remodeling of an A + U-rich RNA element by cation or AUF1 binding.
  J Biol Chem, 276, 38400-38409.  
11179892 J.M.Pérez-Cañadillas, and G.Varani (2001).
Recent advances in RNA-protein recognition.
  Curr Opin Struct Biol, 11, 53-58.  
11376140 X.Manival, L.Ghisolfi-Nieto, G.Joseph, P.Bouvet, and M.Erard (2001).
RNA-binding strategies common to cold-shock domain- and RNA recognition motif-containing proteins.
  Nucleic Acids Res, 29, 2223-2233.  
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.