title: Structural mechanism of nuclear transport mediated by importin β and flexible amphiphilic proteins.
abstract: Karyopherin β family proteins mediate the nuclear/cytoplasmic transport of various proteins through the nuclear pore complex (NPC), although they are substantially larger than the size limit of the NPC.To elucidate the molecular mechanism underlying this paradoxical function, we focused on the unique structures called HEAT repeats, which consist of repetitive amphiphilic α helices. An in vitro transport assay and FRAP analyses demonstrated that not only karyopherin β family proteins but also other proteins with HEAT repeats could pass through the NPC by themselves, and serve as transport mediators for their binding partners. Biochemical and spectroscopic analyses and molecular dynamics simulations of purified HEAT-rich proteins revealed that they interact with hydrophobic groups, including phenyl and alkyl groups, and undergo reversible conformational changes in tertiary structures, but not in secondary structures. These results show that conformational changes in the flexible amphiphilic motifs play a critical role in translocation through the NPC.
authors.affiliation: Graduate School of Biostudies, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: yoshimura@lif.kyoto-u.ac.jp.
authors.forename: Shige H
authors.initials: SH
authors.lastname: Yoshimura
authors.affiliation: Graduate School of Biostudies, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kumeta
authors.affiliation: Graduate School of Biostudies, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Takeyasu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D028884:Karyopherins / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D022022:Nuclear Pore / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism*
chemical_list: D028884:Karyopherins; D028961:beta Karyopherins