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PDBsum entry 2ot8

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protein Protein-protein interface(s) links
Transport protein PDB id
2ot8
Jmol PyMol
Contents
Protein chains
824 a.a. *
17 a.a. *
20 a.a. *
* Residue conservation analysis
PDB id:
2ot8
Name: Transport protein
Title: Karyopherin beta2/transportin-hnrnpm nls complex
Structure: Transportin-1. Chain: a, b. Synonym: importin beta-2, karyopherin beta-2, m9 region interaction protein, mip. Engineered: yes. Heterogeneous nuclear ribonucleoprotein m. Chain: c, d. Fragment: hnrnpm nls fragment (residues 41-70). Synonym: hnrnp m.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: tnpo1, kpnb2, mip1, trn. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: hnrpm.
Resolution:
3.10Å     R-factor:   0.255     R-free:   0.290
Authors: A.E.Cansizoglu,Y.M.Chook
Key ref:
A.E.Cansizoglu et al. (2007). Structure-based design of a pathway-specific nuclear import inhibitor. Nat Struct Biol, 14, 452-454. PubMed id: 17435768 DOI: 10.1038/nsmb1229
Date:
07-Feb-07     Release date:   10-Apr-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q92973  (TNPO1_HUMAN) -  Transportin-1
Seq:
Struc:
 
Seq:
Struc:
898 a.a.
824 a.a.
Protein chain
Pfam   ArchSchema ?
P52272  (HNRPM_HUMAN) -  Heterogeneous nuclear ribonucleoprotein M
Seq:
Struc:
 
Seq:
Struc:
730 a.a.
17 a.a.
Protein chain
Pfam   ArchSchema ?
P52272  (HNRPM_HUMAN) -  Heterogeneous nuclear ribonucleoprotein M
Seq:
Struc:
 
Seq:
Struc:
730 a.a.
20 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     intracellular protein transport   1 term 
  Biochemical function     Ran GTPase binding     1 term  

 

 
DOI no: 10.1038/nsmb1229 Nat Struct Biol 14:452-454 (2007)
PubMed id: 17435768  
 
 
Structure-based design of a pathway-specific nuclear import inhibitor.
A.E.Cansizoglu, B.J.Lee, Z.C.Zhang, B.M.Fontoura, Y.M.Chook.
 
  ABSTRACT  
 
Kapbeta2 (also called transportin) recognizes PY nuclear localization signal (NLS), a new class of NLS with a R/H/Kx((2-5))PY motif. Here we show that Kapbeta2 complexes containing hydrophobic and basic PY-NLSs, as classified by the composition of an additional N-terminal motif, converge in structure only at consensus motifs, which explains ligand diversity. On the basis of these data and complementary biochemical analyses, we designed a Kapbeta2-specific nuclear import inhibitor, M9M.
 
  Selected figure(s)  
 
Figure 1.
(a) Ribbon model of Kap 2 (pink), hnRNP M NLS (magenta) and the 2.5 F[o] – F[c] map (blue). (b) NLSs of hnRNP M (magenta) and hnRNP A1 (2H4M; blue) upon superposition of Kap 2 residues 435–780. Regions of structural similarity are highlighted in yellow. Structurally aligned NLS sequences, C –C distances and inhibitor M9M sequence are shown. (c) Loss of Kap 2-binding energy in alanine mutants of hnRNP A1 (ref.
Figure 2.
(a–c) Coomassie-stained gels of (a) glutathione S-transferase (GST) fusions of hnRNP A1 NLS, hnRNP M NLS and M9M bound to Kap 2 and then dissociated by 0.3–1.6 M RanGTP; (b) GST–hnRNP A1 NLS bound to Kap 2 in the presence of buffer, maltose-binding protein (MBP)–hnRNP A1 NLS, MBP–hnRNP M NLS or MBP-M9M; (c) interactions of GST-Kap 1 with Kap , Kap in the presence of importin- –binding (IBB) domain of Kap , M9M or Kap
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2007, 14, 452-454) copyright 2007.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20649471 J.Heo (2011).
Redox control of GTPases: from molecular mechanisms to functional significance in health and disease.
  Antioxid Redox Signal, 14, 689-724.  
  21401918 L.Gu, T.Tsuji, M.A.Jarboui, G.P.Yeo, N.Sheehy, W.W.Hall, and V.W.Gautier (2011).
Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.
  Retrovirology, 8, 17.  
21139563 M.Grünwald, and F.Bono (2011).
Structure of Importin13-Ubc9 complex: nuclear import and release of a key regulator of sumoylation.
  EMBO J, 30, 427-438.
PDB code: 2xwu
21647358 R.P.Leemann-Zakaryan, S.Pahlich, D.Grossenbacher, and H.Gehring (2011).
Tyrosine Phosphorylation in the C-Terminal Nuclear Localization and Retention Signal (C-NLS) of the EWS Protein.
  Sarcoma, 2011, 218483.  
21109527 Y.Kino, C.Washizu, E.Aquilanti, M.Okuno, M.Kurosawa, M.Yamada, H.Doi, and N.Nukina (2011).
Intracellular localization and splicing regulation of FUS/TLS are variably affected by amyotrophic lateral sclerosis-linked mutations.
  Nucleic Acids Res, 39, 2781-2798.  
20606625 D.Dormann, R.Rodde, D.Edbauer, E.Bentmann, I.Fischer, A.Hruscha, M.E.Than, I.R.Mackenzie, A.Capell, B.Schmid, M.Neumann, and C.Haass (2010).
ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import.
  EMBO J, 29, 2841-2857.  
20818336 R.Pawłowski, E.K.Rajakylä, M.K.Vartiainen, and R.Treisman (2010).
An actin-regulated importin α/β-dependent extended bipartite NLS directs nuclear import of MRTF-A.
  EMBO J, 29, 3448-3458.  
19641022 C.K.Lau, V.A.Delmar, R.C.Chan, Q.Phung, C.Bernis, B.Fichtman, B.A.Rasala, and D.J.Forbes (2009).
Transportin regulates major mitotic assembly events: from spindle to nuclear pore assembly.
  Mol Biol Cell, 20, 4043-4058.  
19339969 X.Dong, A.Biswas, K.E.Süel, L.K.Jackson, R.Martinez, H.Gu, and Y.M.Chook (2009).
Structural basis for leucine-rich nuclear export signal recognition by CRM1.
  Nature, 458, 1136-1141.
PDB code: 3gb8
18532879 K.E.Süel, H.Gu, and Y.M.Chook (2008).
Modular organization and combinatorial energetics of proline-tyrosine nuclear localization signals.
  PLoS Biol, 6, e137.  
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.

 

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