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PDBsum entry 3btr
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protein Protein-protein interface(s) links
Hormone PDB id
3btr

 

 

 

 

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Contents
Protein chains
427 a.a. *
15 a.a. *
Waters ×33
* Residue conservation analysis
PDB id:
3btr
Name: Hormone
Title: Ar-nls:importin-alpha complex
Structure: Importin subunit alpha-2. Chain: c. Fragment: unp residues 70-496. Synonym: karyopherin subunit alpha-2, srp1-alpha, rag cohort protein 1, pendulin, pore targeting complex 58 kda subunit, ptac58, importin alpha p1. Engineered: yes. Androgen receptor. Chain: b.
Source: Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
Resolution:
2.60Å     R-factor:   0.189     R-free:   0.229
Authors: M.L.Cutress,H.C.Whitaker,I.G.Mills,M.Stewart,D.E.Neal
Key ref: M.L.Cutress et al. (2008). Structural basis for the nuclear import of the human androgen receptor. J Cell Sci, 121, 957-968. PubMed id: 18319300
Date:
30-Dec-07     Release date:   30-Dec-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P52293  (IMA1_MOUSE) -  Importin subunit alpha-1 from Mus musculus
Seq:
Struc: 		 
Seq:
Struc: 		529 a.a.
427 a.a.
Protein chain
Pfam   ArchSchema ?
P10275  (ANDR_HUMAN) -  Androgen receptor from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		920 a.a.
15 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
J Cell Sci 121:957-968 (2008)
PubMed id: 18319300  
 
 
Structural basis for the nuclear import of the human androgen receptor.
M.L.Cutress, H.C.Whitaker, I.G.Mills, M.Stewart, D.E.Neal.
 
  ABSTRACT  
 
Ligand-dependent nuclear import is crucial for the function of the androgen receptor (AR) in both health and disease. The unliganded AR is retained in the cytoplasm but, on binding 5alpha-dihydrotestosterone, it translocates into the nucleus and alters transcription of its target genes. Nuclear import of AR is mediated by the nuclear import factor importin-alpha, which functions as a receptor that recognises and binds to specific nuclear localisation signal (NLS) motifs on cargo proteins. We show here that the AR binds to importin-alpha directly, albeit more weakly than the NLS of SV40 or nucleoplasmin. We describe the 2.6-angstroms-resolution crystal structure of the importin-alpha-AR-NLS complex, and show that the AR binds to the major NLS-binding site on importin-alpha in a manner different from most other NLSs. Finally, we have shown that pathological mutations within the NLS of AR that are associated with prostate cancer and androgen-insensitivity syndrome reduce the binding affinity to importin-alpha and, subsequently, retard nuclear import; surprisingly, however, the transcriptional activity of these mutants varies widely. Thus, in addition to its function in the nuclear import of AR, the NLS in the hinge region of AR has a separate, quite distinct role on transactivation, which becomes apparent once nuclear import has been achieved.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21274273 D.N.Lavery, and C.L.Bevan (2011).
Androgen receptor signalling in prostate cancer: the functional consequences of acetylation.
  J Biomed Biotechnol, 2011, 862125.  
21138946 F.Iwamoto, T.Umemoto, K.Motojima, and Y.Fujiki (2011).
Nuclear transport of peroxisome-proliferator activated receptor α.
  J Biochem, 149, 311-319.  
21179018 A.N.Kolodkin, F.J.Bruggeman, N.Plant, M.J.Moné, B.M.Bakker, M.J.Campbell, J.P.van Leeuwen, C.Carlberg, J.L.Snoep, and H.V.Westerhoff (2010).
Design principles of nuclear receptor signaling: how complex networking improves signal transduction.
  Mol Syst Biol, 6, 446.  
20853390 B.Liu, L.Su, J.Geng, J.Liu, and G.Zhao (2010).
Developments in nonsteroidal antiandrogens targeting the androgen receptor.
  ChemMedChem, 5, 1651-1661.  
20701745 J.B.Kelley, A.M.Talley, A.Spencer, D.Gioeli, and B.M.Paschal (2010).
Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors.
  BMC Cell Biol, 11, 63.  
20186458 T.M.Tanner, S.Denayer, B.Geverts, N.Van Tilborgh, S.Kerkhofs, C.Helsen, L.Spans, V.Dubois, A.B.Houtsmuller, F.Claessens, and A.Haelens (2010).
A 629RKLKK633 motif in the hinge region controls the androgen receptor at multiple levels.
  Cell Mol Life Sci, 67, 1919-1927.  
19514019 L.M.McLane, and A.H.Corbett (2009).
Nuclear localization signals and human disease.
  IUBMB Life, 61, 697-706.  
  18612376 F.Claessens, S.Denayer, N.Van Tilborgh, S.Kerkhofs, C.Helsen, and A.Haelens (2008).
Diverse roles of androgen receptor (AR) domains in AR-mediated signaling.
  Nucl Recept Signal, 6, e008.  
18716025 M.Hatayama, T.Tomizawa, K.Sakai-Kato, P.Bouvagnet, S.Kose, N.Imamoto, S.Yokoyama, N.Utsunomiya-Tate, K.Mikoshiba, T.Kigawa, and J.Aruga (2008).
Functional and structural basis of the nuclear localization signal in the ZIC3 zinc finger domain.
  Hum Mol Genet, 17, 3459-3473.
PDB code: 2rpc
18836453 W.Chen, S.S.Lam, H.Srinath, Z.Jiang, J.J.Correia, C.A.Schiffer, K.A.Fitzgerald, K.Lin, and W.E.Royer (2008).
Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5.
  Nat Struct Mol Biol, 15, 1213-1220.
PDB code: 3dsh
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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