title: Structure of importin-beta bound to the IBB domain of importin-alpha.
abstract: Cytosolic proteins bearing a classical nuclear localization signal enter the nucleus bound to a heterodimer of importin-alpha and importin-beta (also called karyopherin-alpha and -beta). The formation of this heterodimer involves the importin-beta-binding (IBB) domain of importin-alpha, a highly basic amino-terminal region of roughly 40 amino-acid residues. Here we report the crystal structure of human importin-beta bound to the IBB domain of importin-alpha, determined at 2.5 A and 2.3 A resolution in two crystal forms. Importin-beta consists of 19 tandemly repeated HEAT motifs and wraps intimately around the IBB domain. The association involves two separate regions of importin-beta, recognizing structurally distinct parts of the IBB domain: an amino-terminal extended moiety and a carboxy-terminal helix. The structure indicates that significant conformational changes occur when importin-beta binds or releases the IBB domain domain and suggests how dissociation of the importin-alpha/beta heterodimer may be achieved upon nuclear entry.
authors.affiliation: European Molecular Biology Laboratory, Grenoble Outstation, France.
authors.forename: G
authors.initials: G
authors.lastname: Cingolani
authors.forename: C
authors.initials: C
authors.lastname: Petosa
authors.forename: K
authors.initials: K
authors.lastname: Weis
authors.forename: C W
authors.initials: CW
authors.lastname: Müller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D019143:Evolution, Molecular; D006801:Humans; D028884:Karyopherins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D020449:Repetitive Sequences, Amino Acid; D020931:ran GTP-Binding Protein
chemical_list: D028884:Karyopherins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D020931:ran GTP-Binding Protein