3BTR

AR-NLS:Importin-alpha complex

Summary for 3BTR

• Entry DOI: 10.2210/pdb3btr/pdb
• Descriptor: Importin subunit alpha-2, Androgen receptor (3 entities in total)
• Functional Keywords: importin-alpha-androgen receptor complex, cytoplasm, nucleus, phosphoprotein, protein transport, transport, disease mutation, dna-binding, lipid-binding, metal-binding, polymorphism, steroid-binding, transcription, transcription regulation, triplet repeat expansion, ubl conjugation, zinc, zinc-finger, hormone
• Biological source: Mus musculus (Mouse); More
• Cellular location: Cytoplasm (By similarity): P52293; Nucleus: P10275
• Total number of polymer chains: 2
• Total formula weight: 47875.92

Authors

Cutress, M.L.,Whitaker, H.C.,Mills, I.G.,Stewart, M.,Neal, D.E. (deposition date: 2007-12-30, release date: 2008-12-30, Last modification date: 2023-11-01)

Primary citation

Cutress, M.L.,Whitaker, H.C.,Mills, I.G.,Stewart, M.,Neal, D.E.
Structural basis for the nuclear import of the human androgen receptor
J.Cell.Sci., 121:957-968, 2008

PubMed 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.

PubMed: 18319300
DOI: 10.1242/jcs.022103

Experimental method

X-RAY DIFFRACTION (2.6 Å)