title: Nuclear import factors importin alpha and importin beta undergo mutually induced conformational changes upon association.
abstract: A heterodimer of importin alpha and importin beta accomplishes the nuclear import of proteins carrying classical nuclear localization signals (NLS). The interaction between the two import factors is mediated by the IBB domain of importin alpha and involves an extended recognition surface as shown by X-ray crystallography. Using a combination of biochemical and biophysical techniques we have investigated the formation of the importin beta:IBB domain complex in solution. Our data suggest that upon binding to the IBB domain, importin beta adopts a compact, proteolytically resistant conformation, while simultaneously the IBB domain folds into an alpha helix. We suggest a model to describe how these dual mutually induced conformational changes may orchestrate the nuclear import of NLS cargo in vivo.
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: G
authors.initials: G
authors.lastname: Cingolani
authors.forename: H A
authors.initials: HA
authors.lastname: Lashuel
authors.forename: L
authors.initials: L
authors.lastname: Gerace
authors.forename: C W
authors.initials: CW
authors.lastname: Müller
mesh_terms: D002942:Circular Dichroism; D003001:Cloning, Molecular; D019281:Dimerization; D006801:Humans; D028884:Karyopherins; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D028884:Karyopherins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins