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PDBsum entry 1n54

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protein ligands Protein-protein interface(s) links
RNA binding protein PDB id
1n54
Jmol
Contents
Protein chains
733 a.a. *
121 a.a. *
Ligands
GOL ×7
Waters ×255
* Residue conservation analysis
PDB id:
1n54
Name: RNA binding protein
Title: Cap binding complex m7gpppg free
Structure: 80 kda nuclear cap binding protein. Chain: a. Synonym: ncbp 80 kda subunit, cap binding protein 80, cbp80 engineered: yes. 20 kda nuclear cap binding protein. Chain: b. Synonym: ncbp 20 kda subunit, cap binding protein 20, cbp20 interacting protein 1, nip1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cbp80. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21. Gene: cbp20.
Biol. unit: Dimer (from PQS)
Resolution:
2.72Å     R-factor:   0.263     R-free:   0.282
Authors: G.Calero,K.Wilson,T.Ly,J.Rios-Steiner,J.Clardy,R.Cerione
Key ref:
G.Calero et al. (2002). Structural basis of m7GpppG binding to the nuclear cap-binding protein complex. Nat Struct Biol, 9, 912-917. PubMed id: 12434151 DOI: 10.1038/nsb874
Date:
04-Nov-02     Release date:   18-Feb-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q09161  (NCBP1_HUMAN) -  Nuclear cap-binding protein subunit 1
Seq:
Struc:
 
Seq:
Struc:
790 a.a.
733 a.a.
Protein chain
Pfam   ArchSchema ?
P52298  (NCBP2_HUMAN) -  Nuclear cap-binding protein subunit 2
Seq:
Struc:
156 a.a.
121 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     plasma membrane   10 terms 
  Biological process     viral reproduction   28 terms 
  Biochemical function     protein binding     7 terms  

 

 
DOI no: 10.1038/nsb874 Nat Struct Biol 9:912-917 (2002)
PubMed id: 12434151  
 
 
Structural basis of m7GpppG binding to the nuclear cap-binding protein complex.
G.Calero, K.F.Wilson, T.Ly, J.L.Rios-Steiner, J.C.Clardy, R.A.Cerione.
 
  ABSTRACT  
 
The 7-methyl guanosine cap structure of RNA is essential for key aspects of RNA processing, including pre-mRNA splicing, 3' end formation, U snRNA transport, nonsense-mediated decay and translation. Two cap-binding proteins mediate these effects: cytosolic eIF-4E and nuclear cap-binding protein complex (CBC). The latter consists of a CBP20 subunit, which binds the cap, and a CBP80 subunit, which ensures high-affinity cap binding. Here we report the 2.1 A resolution structure of human CBC with the cap analog m7GpppG, as well as the structure of unliganded CBC. Comparisons between these structures indicate that the cap induces substantial conformational changes within the N-terminal loop of CBP20, enabling Tyr 20 to join Tyr 43 in pi-pi stacking interactions with the methylated guanosine base. CBP80 stabilizes the movement of the N-terminal loop of CBP20 and locks the CBC into a high affinity cap-binding state. The structure for the CBC bound to m7GpppG highlights interesting similarities and differences between CBC and eIF-4E, and provides insights into the regulatory mechanisms used by growth factors and other extracellular stimuli to influence the cap-binding state of the CBC.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Interactions of CBP20 with m7GpppG. a, Stereo depiction of the electron density (2F[o] - F[c]) simulated annealing omit map calculated omitting m7GpppG and contoured at 3.0 . The average B-factors for 7-methylated guanosine triphosphate and the nonmethylated guanosine are 45 ┼2 and 79 ┼2, respectively. b, Surface electrostatic representation calculated with SPOCK (http://quorum.tamu.edu/spock/) for the m7GpppG-binding cavity. The roof and part of the floor of the cavity are formed by residues Tyr 20 and Tyr 43, respectively. The electrostatic potential inside the cavity neutralizes the charges of the guanosine base and the phosphate oxygen atoms. c, Ball-and-stick representation of - stacking and degree of overlap between Tyr 20, m7GpppG and Tyr 43. Tyr 20 makes two hydrogen bonds with 7-methyl guanosine: Tyr 20(OH) -O1B = 2.81 ┼ and Tyr 20(OH) -O2 = 2.95 ┼ (see text). The left and the right depictions are related by a 90░ rotation along the plane perpendicular to the page. d, Schematic representation using LigplOt36 of the hydrogen bond network stabilizing m7GpppG. Residue color is N-terminus (magenta), RNP domain (gray) and C-terminus (green). Red arches indicate residues involved in van der Waals contacts. Numbers indicate distances in (┼).
Figure 4.
Figure 4. Surface (CBP80) and ribbon (CBP20) representation of the CBC to illustrate the stabilization of the N-terminal hinge of CBP20 by CBP80. The N-terminal region of CBP20 (residues Ser 11, Asp 12 and Ser 13 shown in magenta) crosses through a 'binding grove' formed by residues Lys 327 and Glu 328 of CBP80 (cyan), making several contacts that allow the hinged motion of residues 16 -29 of CBP20 in loop 2 - 3. The N-terminal region of CBP80 is blue. The inset shows these interactions in detail, including the hydrogen bonds Lys 327(NZ) -Leu 9(O) = 3.3 ┼, Glu 328(OE2) -Ser 11(OG) = 2.93 ┼ and Glu 328(OE2) -Ser 13(N) = 2.74 ┼.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 912-917) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21143728 K.Jäger, A.Fábián, G.Tompa, C.Deák, M.Höhn, A.Olmedilla, B.Barnabás, and I.Papp (2011).
New phenotypes of the drought-tolerant cbp20 Arabidopsis thaliana mutant have changed epidermal morphology.
  Plant Biol (Stuttg), 13, 78-84.  
20535623 K.Ruszczyńska-Bartnik, M.Maciejczyk, and R.Stolarski (2011).
Dynamical insight into Caenorhabditis elegans eIF4E recognition specificity for mono-and trimethylated structures of mRNA 5' cap.
  J Mol Model, 17, 727-737.  
21075799 S.Lahudkar, A.Shukla, P.Bajwa, G.Durairaj, N.Stanojevic, and S.R.Bhaumik (2011).
The mRNA cap-binding complex stimulates the formation of pre-initiation complex at the promoter via its interaction with Mot1p in vivo.
  Nucleic Acids Res, 39, 2188-2209.  
20360394 J.Chang, B.Schwer, and S.Shuman (2010).
Mutational analyses of trimethylguanosine synthase (Tgs1) and Mud2: proteins implicated in pre-mRNA splicing.
  RNA, 16, 1018-1031.  
20639534 M.F.Soulière, J.P.Perreault, and M.Bisaillon (2010).
Insights into the molecular determinants involved in cap recognition by the vaccinia virus D10 decapping enzyme.
  Nucleic Acids Res, 38, 7599-7610.  
19453442 D.Kierzkowski, M.Kmieciak, P.Piontek, P.Wojtaszek, Z.Szweykowska-Kulinska, and A.Jarmolowski (2009).
The Arabidopsis CBP20 targets the cap-binding complex to the nucleus, and is stabilized by CBP80.
  Plant J, 59, 814-825.  
19884259 H.Sato, and L.E.Maquat (2009).
Remodeling of the pioneer translation initiation complex involves translation and the karyopherin importin beta.
  Genes Dev, 23, 2537-2550.  
19644445 R.Li, H.Zhang, W.Yu, Y.Chen, B.Gui, J.Liang, Y.Wang, L.Sun, X.Yang, Y.Zhang, L.Shi, Y.Li, and Y.Shang (2009).
ZIP: a novel transcription repressor, represses EGFR oncogene and suppresses breast carcinogenesis.
  EMBO J, 28, 2763-2776.  
19668212 S.M.Dias, K.F.Wilson, K.S.Rojas, A.L.Ambrosio, and R.A.Cerione (2009).
The molecular basis for the regulation of the cap-binding complex by the importins.
  Nat Struct Mol Biol, 16, 930-937.
PDB codes: 3fex 3fey
18515081 A.Cléry, M.Blatter, and F.H.Allain (2008).
RNA recognition motifs: boring? Not quite.
  Curr Opin Struct Biol, 18, 290-298.  
18369367 C.F.Woeller, M.Gaspari, O.Isken, and L.E.Maquat (2008).
NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA.
  EMBO Rep, 9, 446-451.  
18982294 M.Kvaratskhelia, and S.F.Grice (2008).
Structural analysis of protein-RNA interactions with mass spectrometry.
  Methods Mol Biol, 488, 213-219.  
18186485 R.Worch, and R.Stolarski (2008).
Stacking efficiency and flexibility analysis of aromatic amino acids in cap-binding proteins.
  Proteins, 71, 2026-2037.  
18641416 T.Nagata, S.Suzuki, R.Endo, M.Shirouzu, T.Terada, M.Inoue, T.Kigawa, N.Kobayashi, P.Güntert, A.Tanaka, Y.Hayashizaki, Y.Muto, and S.Yokoyama (2008).
The RRM domain of poly(A)-specific ribonuclease has a noncanonical binding site for mRNA cap analog recognition.
  Nucleic Acids Res, 36, 4754-4767.
PDB code: 2rok
17693554 A.Busch, J.Lacal, A.Martos, J.L.Ramos, and T.Krell (2007).
Bacterial sensor kinase TodS interacts with agonistic and antagonistic signals.
  Proc Natl Acad Sci U S A, 104, 13774-13779.  
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
17524464 M.Kiriakidou, G.S.Tan, S.Lamprinaki, M.De Planell-Saguer, P.T.Nelson, and Z.Mourelatos (2007).
An mRNA m7G cap binding-like motif within human Ago2 represses translation.
  Cell, 129, 1141-1151.  
17785461 P.Nilsson, N.Henriksson, A.Niedzwiecka, N.A.Balatsos, K.Kokkoris, J.Eriksson, and A.Virtanen (2007).
A multifunctional RNA recognition motif in poly(A)-specific ribonuclease with cap and poly(A) binding properties.
  J Biol Chem, 282, 32902-32911.  
16317009 N.A.Balatsos, P.Nilsson, C.Mazza, S.Cusack, and A.Virtanen (2006).
Inhibition of mRNA deadenylation by the nuclear cap binding complex (CBC).
  J Biol Chem, 281, 4517-4522.  
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.  
15920472 A.Strasser, A.Dickmanns, R.Lührmann, and R.Ficner (2005).
Structural basis for m3G-cap-mediated nuclear import of spliceosomal UsnRNPs by snurportin1.
  EMBO J, 24, 2235-2243.
PDB code: 1xk5
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.  
15743819 H.Li, and C.Tschudi (2005).
Novel and essential subunits in the 300-kilodalton nuclear cap binding complex of Trypanosoma brucei.
  Mol Cell Biol, 25, 2216-2226.  
15597333 J.Tang, H.Naitow, N.A.Gardner, A.Kolesar, L.Tang, R.B.Wickner, and J.E.Johnson (2005).
The structural basis of recognition and removal of cellular mRNA 7-methyl G 'caps' by a viral capsid protein: a unique viral response to host defense.
  J Mol Recognit, 18, 158-168.  
15882623 P.F.Cho, F.Poulin, Y.A.Cho-Park, I.B.Cho-Park, J.D.Chicoine, P.Lasko, and N.Sonenberg (2005).
A new paradigm for translational control: inhibition via 5'-3' mRNA tethering by Bicoid and the eIF4E cognate 4EHP.
  Cell, 121, 411-423.  
16043498 R.Worch, A.Niedzwiecka, J.Stepinski, C.Mazza, M.Jankowska-Anyszka, E.Darzynkiewicz, S.Cusack, and R.Stolarski (2005).
Specificity of recognition of mRNA 5' cap by human nuclear cap-binding complex.
  RNA, 11, 1355-1363.  
15601771 A.Kentsis, I.Topisirovic, B.Culjkovic, L.Shao, and K.L.Borden (2004).
Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap.
  Proc Natl Acad Sci U S A, 101, 18105-18110.  
15153109 B.Joshi, A.Cameron, and R.Jagus (2004).
Characterization of mammalian eIF4E-family members.
  Eur J Biochem, 271, 2189-2203.  
15362228 N.Cougot, E.van Dijk, S.Babajko, and B.Séraphin (2004).
'Cap-tabolism'.
  Trends Biochem Sci, 29, 436-444.  
12923259 J.Jemielity, T.Fowler, J.Zuberek, J.Stepinski, M.Lewdorowicz, A.Niedzwiecka, R.Stolarski, E.Darzynkiewicz, and R.E.Rhoads (2003).
Novel "anti-reverse" cap analogs with superior translational properties.
  RNA, 9, 1108-1122.  
12972047 J.M.Kuhn, and J.I.Schroeder (2003).
Impacts of altered RNA metabolism on abscisic acid signaling.
  Curr Opin Plant Biol, 6, 463-469.  
12805428 N.Saha, S.Shuman, and B.Schwer (2003).
Yeast-based genetic system for functional analysis of poxvirus mRNA cap methyltransferase.
  J Virol, 77, 7300-7307.  
12646557 P.Fechter, L.Mingay, J.Sharps, A.Chambers, E.Fodor, and G.G.Brownlee (2003).
Two aromatic residues in the PB2 subunit of influenza A RNA polymerase are crucial for cap binding.
  J Biol Chem, 278, 20381-20388.  
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.