PDBsum entry 2bpt

Go to PDB code: 
protein Protein-protein interface(s) links
Nuclear transport PDB id
Protein chains
860 a.a. *
29 a.a. *
Waters ×752
* Residue conservation analysis
PDB id:
Name: Nuclear transport
Title: Structure of the nup1p:kap95p complex
Structure: Importin beta-1 subunit. Chain: a. Synonym: karyopherin beta-1 subunit, importin 95, kap95p. Engineered: yes. Nucleoporin nup1. Chain: b. Fragment: residues 974-1012. Synonym: nuclear pore protein nup1, nup1p. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
1.99Å     R-factor:   0.174     R-free:   0.231
Authors: S.M.Liu,M.Stewart
Key ref:
S.M.Liu and M.Stewart (2005). Structural basis for the high-affinity binding of nucleoporin Nup1p to the Saccharomyces cerevisiae importin-beta homologue, Kap95p. J Mol Biol, 349, 515-525. PubMed id: 15878174 DOI: 10.1016/j.jmb.2005.04.003
25-Apr-05     Release date:   19-May-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q06142  (IMB1_YEAST) -  Importin subunit beta-1
861 a.a.
860 a.a.*
Protein chain
Pfam   ArchSchema ?
P20676  (NUP1_YEAST) -  Nucleoporin NUP1
1076 a.a.
29 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   5 terms 
  Biological process     transport   10 terms 
  Biochemical function     protein binding     4 terms  


DOI no: 10.1016/j.jmb.2005.04.003 J Mol Biol 349:515-525 (2005)
PubMed id: 15878174  
Structural basis for the high-affinity binding of nucleoporin Nup1p to the Saccharomyces cerevisiae importin-beta homologue, Kap95p.
S.M.Liu, M.Stewart.
Macromolecules are transported across the nuclear envelope most frequently by karyopherin/importin-beta superfamily members that are constructed from HEAT repeats. Transport of Kap95p (yeast importin-beta), the principal carrier for protein import, through nuclear pore complexes is facilitated by interactions with nucleoporins containing FG repeats. However, Nup1p interacts more strongly with Kap95p than other FG-nucleoporins. To establish the basis of this increased affinity, we determined the structure of Kap95p complexed with Nup1p residues 963-1076 that contain the high-affinity Kap95p binding site. Nup1p binds Kap95p at three sites between the outer A-helices of HEAT repeats 5, 6, 7 and 8. At each site, phenylalanine residues from Nup1p are buried in hydrophobic depressions between adjacent HEAT repeats. Although the Nup1p and generic FG-nucleoporin binding sites on Kap95p overlap, Nup1p binding differs markedly and has contributions from additional hydrophobic residues, together with interactions generated by the intimate contact of the linker between Nup1 residues 977-987 with Kap95p. The length and composition of this linker is crucial and suggests how differences in affinity for Kap95p both between and within FG-nucleoporins arise.
  Selected figure(s)  
Figure 4.
Figure 4. Nucleoporin binding to Kap95p and impor- tin-b. (a) Overview of the three Nup1p binding sites on Kap95p, showing key hydrophobic interactions. Each site involves a Phe ring and an additional hydrophobic side- chain (Pro or Ile) inserting into a shallow hydrophobic surface depression formed between adjacent HEAT repeats (blue). There are also hydrophobic interactions in the linker between sites 1 and 2, primarily involving Pro983, so that sites 1 and 2 tend to merge to generate a horseshoe-shaped hydrophobic surface on Kap95p. (b) Overview of the interaction between importin-b and a construct containing five FxFG repeats from Nsp1p. 7 The major binding site (involving Phe14 and Phe17) is similar to Nup1p binding site 3 on Kap95p (involving Ile1007 and Phe1008) and involves a hydrophobic surface depression (blue). There is also a secondary site (involv- ing Phe46 and Phe48) that has some similarity to Nup1p binding site 2 on Kap95p. Overall, the binding of the Nsp1p FxFG repeats to importin-b is less extensive and less intimate than that seen with Nup1p on Kap95p and does not have any major contribution from residues outside the FxFG cores.
Figure 5.
Figure 5. Kap95p:Nup1p inter- action interface. This is a schematic illustration of the interactions between Nup1p (red) and HEAT repeats 5--8 of Kap95p. Hydro- phobic interactions are shown as continuous lines and H-bonds as broken lines. The interaction at all three sites was dominated by hydrophobic interactions involv- ing the aromatic ring of a Phe with secondary contributions from an adjacent hydrophobic resi- due. Thus, at site 1, the interaction involved Phe977 and Pro979; at site 2, Phe987 and Ile985; and, at site 3, Phe1008 and Ile1007 (however, because the density was weaker in this region and the Nup1p sequence is repetitive, these may have been Phe1027 and Ile1026). There was also a hydrophobic interaction between Pro983 of Nup1p and HEAT repeat 7. In addition to the hydrophobic interactions, at each site there were also one or two H-bonds to the peptide backbone of Nup1p.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 349, 515-525) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20826343 J.K.Forwood, A.Lange, U.Zachariae, M.Marfori, C.Preast, H.Grubmüller, M.Stewart, A.H.Corbett, and B.Kobe (2010).
Quantitative structural analysis of importin-β flexibility: paradigm for solenoid protein structures.
  Structure, 18, 1171-1183.
PDB code: 3nd2
20368455 J.Ma, and W.Yang (2010).
Three-dimensional distribution of transient interactions in the nuclear pore complex obtained from single-molecule snapshots.
  Proc Natl Acad Sci U S A, 107, 7305-7310.  
20421988 L.J.Colwell, M.P.Brenner, and K.Ribbeck (2010).
Charge as a selection criterion for translocation through the nuclear pore complex.
  PLoS Comput Biol, 6, e1000747.  
20409487 L.Miao, and K.Schulten (2010).
Probing a structural model of the nuclear pore complex channel through molecular dynamics.
  Biophys J, 98, 1658-1667.  
20848643 M.T.Murakami, M.L.Sforça, J.L.Neves, J.H.Paiva, M.N.Domingues, A.L.Pereira, A.C.Zeri, and C.E.Benedetti (2010).
The repeat domain of the type III effector protein PthA shows a TPR-like structure and undergoes conformational changes upon DNA interaction.
  Proteins, 78, 3386-3395.  
20016008 Y.Ogawa, Y.Miyamoto, M.Asally, M.Oka, Y.Yasuda, and Y.Yoneda (2010).
Two isoforms of Npap60 (Nup50) differentially regulate nuclear protein import.
  Mol Biol Cell, 21, 630-638.  
19783821 B.Loll, M.Gebhardt, E.Wahle, and A.Meinhart (2009).
Crystal structure of the EndoG/EndoGI complex: mechanism of EndoG inhibition.
  Nucleic Acids Res, 37, 7312-7320.
PDB code: 3ism
19680225 B.Naim, D.Zbaida, S.Dagan, R.Kapon, and Z.Reich (2009).
Cargo surface hydrophobicity is sufficient to overcome the nuclear pore complex selectivity barrier.
  EMBO J, 28, 2697-2705.  
18984568 K.F.Pulliam, M.B.Fasken, L.M.McLane, J.V.Pulliam, and A.H.Corbett (2009).
The Classical Nuclear Localization Signal Receptor, Importin-{alpha}, Is Required for Efficient Transition Through the G1/S Stage of the Cell Cycle in Saccharomyces cerevisiae.
  Genetics, 181, 105-118.  
19801417 L.J.Terry, and S.R.Wente (2009).
Flexible gates: dynamic topologies and functions for FG nucleoporins in nucleocytoplasmic transport.
  Eukaryot Cell, 8, 1814-1827.  
19278659 L.Miao, and K.Schulten (2009).
Transport-related structures and processes of the nuclear pore complex studied through molecular dynamics.
  Structure, 17, 449-459.  
19748337 S.G.Brohawn, J.R.Partridge, J.R.Whittle, and T.U.Schwartz (2009).
The nuclear pore complex has entered the atomic age.
  Structure, 17, 1156-1168.  
18562297 C.Sun, W.Yang, L.C.Tu, and S.M.Musser (2008).
Single-molecule measurements of importin alpha/cargo complex dissociation at the nuclear pore.
  Proc Natl Acad Sci U S A, 105, 8613-8618.  
18228033 R.Y.Lim, U.Aebi, and B.Fahrenkrog (2008).
Towards reconciling structure and function in the nuclear pore complex.
  Histochem Cell Biol, 129, 105-116.  
18845677 S.Otsuka, S.Iwasaka, Y.Yoneda, K.Takeyasu, and S.H.Yoshimura (2008).
Individual binding pockets of importin-beta for FG-nucleoporins have different binding properties and different sensitivities to RanGTP.
  Proc Natl Acad Sci U S A, 105, 16101-16106.  
18547523 U.Zachariae, and H.Grubmüller (2008).
Importin-beta: structural and dynamic determinants of a molecular spring.
  Structure, 16, 906-915.  
17630825 A.Zilman, S.Di Talia, B.T.Chait, M.P.Rout, and M.O.Magnasco (2007).
Efficiency, Selectivity, and Robustness of Nucleocytoplasmic Transport.
  PLoS Comput Biol, 3, e125.  
18046406 F.Alber, S.Dokudovskaya, L.M.Veenhoff, W.Zhang, J.Kipper, D.Devos, A.Suprapto, O.Karni-Schmidt, R.Williams, B.T.Chait, A.Sali, and M.P.Rout (2007).
The molecular architecture of the nuclear pore complex.
  Nature, 450, 695-701.  
17182855 K.J.Ryan, Y.Zhou, and S.R.Wente (2007).
The karyopherin Kap95 regulates nuclear pore complex assembly into intact nuclear envelopes in vivo.
  Mol Biol Cell, 18, 886-898.  
17287812 M.Stewart (2007).
Molecular mechanism of the nuclear protein import cycle.
  Nat Rev Mol Cell Biol, 8, 195-208.  
17615301 S.Sistla, J.V.Pang, C.X.Wang, and D.Balasundaram (2007).
Multiple conserved domains of the nucleoporin Nup124p and its orthologs Nup1p and Nup153 are critical for nuclear import and activity of the fission yeast Tf1 retrotransposon.
  Mol Biol Cell, 18, 3692-3708.  
17698002 T.A.Isgro, and K.Schulten (2007).
Cse1p-binding dynamics reveal a binding pattern for FG-repeat nucleoporins on transport receptors.
  Structure, 15, 977-991.  
16421734 A.S.Madrid, and K.Weis (2006).
Nuclear transport is becoming crystal clear.
  Chromosoma, 115, 98.  
16461911 D.Devos, S.Dokudovskaya, R.Williams, F.Alber, N.Eswar, B.T.Chait, M.P.Rout, and A.Sali (2006).
Simple fold composition and modular architecture of the nuclear pore complex.
  Proc Natl Acad Sci U S A, 103, 2172-2177.  
16567089 E.Conti, C.W.Müller, and M.Stewart (2006).
Karyopherin flexibility in nucleocytoplasmic transport.
  Curr Opin Struct Biol, 16, 237-244.  
16631361 R.Y.Lim, and B.Fahrenkrog (2006).
The nuclear pore complex up close.
  Curr Opin Cell Biol, 18, 342-347.  
16402261 R.Y.Lim, U.Aebi, and D.Stoffler (2006).
From the trap to the basket: getting to the bottom of the nuclear pore complex.
  Chromosoma, 115, 15-26.  
16338402 R.Y.Lim, and U.Aebi (2005).
In silico access to the nuclear pore complex.
  Structure, 13, 1741-1743.  
16338415 T.A.Isgro, and K.Schulten (2005).
Binding dynamics of isolated nucleoporin repeat regions to importin-beta.
  Structure, 13, 1869-1879.  
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.