title: Molecular architecture of the active mitochondrial protein gate.
abstract: Mitochondria fulfill central functions in cellular energetics, metabolism, and signaling. The outer membrane translocator complex (the TOM complex) imports most mitochondrial proteins, but its architecture is unknown. Using a cross-linking approach, we mapped the active translocator down to single amino acid residues, revealing different transport paths for preproteins through the Tom40 channel. An N-terminal segment of Tom40 passes from the cytosol through the channel to recruit chaperones from the intermembrane space that guide the transfer of hydrophobic preproteins. The translocator contains three Tom40 β-barrel channels sandwiched between a central α-helical Tom22 receptor cluster and external regulatory Tom proteins. The preprotein-translocating trimeric complex exchanges with a dimeric isoform to assemble new TOM complexes. Dynamic coupling of α-helical receptors, β-barrel channels, and chaperones generates a versatile machinery that transports about 1000 different proteins.
authors.affiliation: Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria 3800, Australia. Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Shiota
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Imai
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Jian
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Hewitt
authors.affiliation: Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Khershing
authors.initials: K
authors.lastname: Tan
authors.affiliation: Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Shen
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sakiyama
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukasawa
authors.affiliation: Department of Biochemistry and Biophysics and Science for Life Laboratory, Stockholm University, Box 1031, 17121 Solna, Sweden.
authors.forename: Sikander
authors.initials: S
authors.lastname: Hayat
authors.affiliation: Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Kamiya
authors.affiliation: Department of Biochemistry and Biophysics and Science for Life Laboratory, Stockholm University, Box 1031, 17121 Solna, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Elofsson
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tomii
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Paul
authors.initials: P
authors.lastname: Horton
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, 79104 Freiburg, Germany. Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Wiedemann
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, 79104 Freiburg, Germany. Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.affiliation: Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Trevor
authors.initials: T
authors.lastname: Lithgow
authors.affiliation: Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan. Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Endo
mesh_terms: D000595:Amino Acid Sequence; D003600:Cytosol / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C090857:TOM22 protein, S cerevisiae; C066555:Tom40 protein, S cerevisiae