Tom20 recognizes mitochondrial presequences through dynamic equilibrium among multiple bound states

Takashi Saitoh, Mayumi Igura, Takayuki Obita, Toyoyuki Ose, Rieko Kojima, Katsumi Maenaka, Toshiya Endo, Daisuke Kohda

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    121 Citations (Scopus)


    Most mitochondrial proteins are synthesized in the cytosol and imported into mitochondria. The N-terminal presequences of mitochondrial-precursor proteins contain a diverse consensus motif (φχχφφ, φ is hydrophobic and χ is any amino acid), which is recognized by the Tom20 protein on the mitochondrial surface. To reveal the structural basis of the broad selectivity of Tom20, the Tom20-presequence complex was crystallized. Tethering a presequence peptide to Tom20 through a disulfide bond was essential for crystallization. Unexpectedly, the two crystals with different linker designs provided unique relative orientations of the presequence with respect to Tom20, and neither configuration could fully account for the hydrophobic preference at the three hydrophobic positions of the consensus motif. We propose the existence of a dynamic equilibrium in solution among multiple states including the two bound states. In accordance, NMR 15N relaxation analyses suggested motion on a sub-millisecond timescale at the Tom20-presequence interface. We suggest that the dynamic, multiple-mode interaction is the molecular mechanism facilitating the broadly selective specificity of the Tom20 receptor toward diverse mitochondrial presequences.

    Original languageEnglish
    Pages (from-to)4777-4787
    Number of pages11
    JournalEMBO Journal
    Issue number22
    Publication statusPublished - Nov 14 2007

    All Science Journal Classification (ASJC) codes

    • Neuroscience(all)
    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)


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