title: Structural Biology and Regulation of Protein Import into the Nucleus.
abstract: Proteins are translated in the cytoplasm, but many need to access the nucleus to perform their functions. Understanding how these nuclear proteins are transported through the nuclear envelope and how the import processes are regulated is therefore an important aspect of understanding cell function. Structural biology has played a key role in understanding the molecular events during the transport processes and their regulation, including the recognition of nuclear targeting signals by the corresponding receptors. Here, we review the structural basis of the principal nuclear import pathways and the molecular basis of their regulation. The pathways involve transport factors that are members of the β-karyopherin family, which can bind cargo directly (e.g., importin-β, transportin-1, transportin-3, importin-13) or through adaptor proteins (e.g., importin-α, snurportin-1, symportin-1), as well as unrelated transport factors such as Hikeshi, involved in the transport of heat-shock proteins, and NTF2, involved in the transport of RanGDP. Solenoid proteins feature prominently in these pathways. Nuclear transport factors recognize nuclear targeting signals on the cargo proteins, including the classical nuclear localization signals, recognized by the adaptor importin-α, and the PY nuclear localization signals, recognized by transportin-1. Post-translational modifications, particularly phosphorylation, constitute key regulatory mechanisms operating in these pathways.
authors.affiliation: The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales Faculty of Medicine, Darlinghurst, NSW 2010, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Christie
authors.affiliation: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Chiung-Wen
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest H-1117, Hungary; Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest H-1111, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Róna
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Smith
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Stewart
authors.affiliation: Department of Physics and Biophysics, Institute of Biosciences, Universidade Estadual Paulista, Botucatu, São Paulo 18618-000, Brazil.
authors.forename: Agnes A S
authors.initials: AA
authors.lastname: Takeda
authors.affiliation: Department of Physics and Biophysics, Institute of Biosciences, Universidade Estadual Paulista, Botucatu, São Paulo 18618-000, Brazil.
authors.forename: Marcos R M
authors.initials: MR
authors.lastname: Fontes
authors.affiliation: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom.
authors.forename: Murray
authors.initials: M
authors.lastname: Stewart
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest H-1117, Hungary; Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest H-1111, Hungary.
authors.forename: Beáta G
authors.initials: BG
authors.lastname: Vértessy
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.
authors.forename: Jade K
authors.initials: JK
authors.lastname: Forwood
authors.affiliation: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: b.kobe@uq.edu.au.
authors.forename: Bostjan
authors.initials: B
authors.lastname: Kobe
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D022022:Nuclear Pore / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D028961:beta Karyopherins / Q000378:metabolism
chemical_list: D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D028961:beta Karyopherins
keywords: beta-karyopherin; crystal structure; importin-alpha; nuclear localization signal (NLS); nucleocytoplasmic transport