title: Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha.
abstract: Importin alpha is the nuclear import receptor that recognizes classical monopartite and bipartite nuclear localization signals (NLSs). The structure of mouse importin alpha has been determined at 2.5 A resolution. The structure shows a large C-terminal domain containing armadillo repeats, and a less structured N-terminal importin beta-binding domain containing an internal NLS bound to the NLS-binding site. The structure explains the regulatory switch between the cytoplasmic, high-affinity form, and the nuclear, low-affinity form for NLS binding of the nuclear import receptor predicted by the current models of nuclear import. Importin beta conceivably converts the low- to high-affinity form by binding to a site overlapping the autoinhibitory sequence. The structure also has implications for understanding NLS recognition, and the structures of armadillo and HEAT repeats.
authors: Structural Biology Laboratory, St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia. B.Kobe@medicine.unimelb.edu.au
authors: B
authors: B
authors: Kobe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D028884:Karyopherins; D008322:Mammals; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015003:Yeasts / Q000737:chemistry
chemical_list: D005656:Fungal Proteins; D028884:Karyopherins; D009687:Nuclear Proteins