title: A presequence-binding groove in Tom70 supports import of Mdl1 into mitochondria.
abstract: The translocase of the outer mitochondrial membrane (TOM complex) is the general entry gate into mitochondria for almost all imported proteins. A variety of specific receptors allow the TOM complex to recognize targeting signals of various precursor proteins that are transported along different import pathways. Aside from the well-characterized presequence receptors Tom20 and Tom22 a third TOM receptor, Tom70, binds proteins of the carrier family containing multiple transmembrane segments. Here we demonstrate that Tom70 directly binds to presequence peptides using a dedicated groove. A single point mutation in the cavity of this pocket (M551R) reduces the presequence binding affinity of Tom70 ten-fold and selectively impairs import of the presequence-containing precursor Mdl1 but not the ADP/ATP carrier (AAC). Hence Tom70 contributes to the presequence import pathway by recognition of the targeting signal of the Mdl1 precursor.
authors.affiliation: Institute of Cellular Biochemistry, University Medical Center Göttingen, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melin
authors.affiliation: Department of Molecular Biology, University Medical Center Göttingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Kilisch
authors.affiliation: Department of Molecular Structural Biology, University of Göttingen, Germany.
authors.forename: Piotr
authors.initials: P
authors.lastname: Neumann
authors.affiliation: Institute of Cellular Biochemistry, University Medical Center Göttingen, Germany.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Lytovchenko
authors.affiliation: Institute of Cellular Biochemistry, University Medical Center Göttingen, Germany.
authors.forename: Ridhima
authors.initials: R
authors.lastname: Gomkale
authors.affiliation: Institute of Cellular Biochemistry, University Medical Center Göttingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schendzielorz
authors.affiliation: Institute of Cellular Biochemistry, University Medical Center Göttingen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schmidt
authors.affiliation: Proteomics Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Liepold
authors.affiliation: Department of Molecular Structural Biology, University of Göttingen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Ficner
authors.affiliation: Proteomics Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Jahn
authors.affiliation: Institute of Cellular Biochemistry, University Medical Center Göttingen, Germany; Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. Electronic address: Peter.Rehling@medizin.uni-goettingen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.affiliation: Institute of Cellular Biochemistry, University Medical Center Göttingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008958:Models, Molecular; D030781:Organisms, Genetically Modified; D011485:Protein Binding / Q000235:genetics; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics; D017433:Protein Structure, Secondary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; C490069:MDL1 protein, S cerevisiae; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D029701:Saccharomyces cerevisiae Proteins; C489039:TOM70 protein, S cerevisiae
keywords: Mitochondria; Presequence; Protein import; Tom70