Abstract
The biogenesis of mitochondria depends on the import of hundreds of preproteins. N-terminal matrix-targeting signals (MTSs) direct preproteins to the surface receptors Tom20, Tom22, and Tom70. In this study, we show that many preproteins contain additional internal MTS-like signals (iMTS-Ls) in their mature region that share the characteristic properties of presequences. These features allow the in silico prediction of iMTS-Ls. Using Atp1 as model substrate, we show that iMTS-Ls mediate the binding to Tom70 and have the potential to target the protein to mitochondria if they are presented at its N terminus. The import of preproteins with high iMTS-L content is significantly impaired in the absence of Tom70, whereas preproteins with low iMTS-L scores are less dependent on Tom70. We propose a stepping stone model according to which the Tom70-mediated interaction with internal binding sites improves the import competence of preproteins and increases the efficiency of their translocation into the mitochondrial matrix.
© 2018 Backes et al.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Chaperonin 60 / chemistry
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Chaperonin 60 / genetics
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Chaperonin 60 / metabolism
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Kinetics
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Mitochondria / metabolism*
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Mitochondrial Membrane Transport Proteins / chemistry
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Mitochondrial Membrane Transport Proteins / genetics
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Mitochondrial Membrane Transport Proteins / metabolism*
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Mitochondrial Precursor Protein Import Complex Proteins
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Models, Biological
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Protein Binding
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Protein Interaction Domains and Motifs*
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Protein Precursors / chemistry
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Protein Precursors / genetics
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Protein Precursors / metabolism*
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Protein Sorting Signals*
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Protein Transport
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Proteomics / methods
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
Substances
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Chaperonin 60
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HSP60 protein, S cerevisiae
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Precursor Protein Import Complex Proteins
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Protein Precursors
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Protein Sorting Signals
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Saccharomyces cerevisiae Proteins
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TOM70 protein, S cerevisiae
Associated data
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GENBANK/CAB11207
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GENBANK/AAH11384
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GENBANK/AEE76842
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GENBANK/EDP07337
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GENBANK/ABF67773
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GENBANK/AMS12509
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RefSeq/NP_009453
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RefSeq/NP_013360
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RefSeq/XP_454248
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RefSeq/XP_455510
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RefSeq/XP_449761
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RefSeq/XP_448482
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RefSeq/NP_592894
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RefSeq/NP_726243
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RefSeq/NP_511115
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RefSeq/XP_001691353
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SWISSPROT/P10809
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SWISSPROT/P92549