title: Mitochondrial protein import: reversible binding of the presequence at the trans side of the outer membrane drives partial translocation and unfolding.
abstract: The mechanism of translocation of matrix-targeted, cleavable preproteins across the mitochondrial outer membrane was studied using purified outer membrane vesicles. The N-terminal presequence interacts in a sequential and reversible fashion with two specific binding sites. The first one is provided by protease-sensitive receptors on the surface of the membrane (cis site); the second one is located at the inner face of the outer membrane (trans site). Binding to the trans site drives translocation of the N-terminal portion of the preprotein and, at the same time, unfolding of its mature part. We suggest that the outer membrane protein import machinery forms a translocation channel that permits reversible sliding of preproteins and prevents their lateral aggregation in the membrane. Although translocation can be initiated by the outer membrane, its completion requires coupling to the energetic system of the inner membrane. Our data assign an essential role to the presequence, not only for efficient targeting, but also for the translocation step.
authors: Institut für Physiologische Chemie, Physikalische Biochemie und Zellbiologie, Universität München, Federal Republic of Germany.
authors: A
authors: A
authors: Mayer
authors: W
authors: W
authors: Neupert
authors: R
authors: R
authors: Lill
mesh_terms: D001665:Binding Sites; D002458:Cell Fractionation; D007425:Intracellular Membranes / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D017510:Protein Folding; D011498:Protein Precursors / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000096122:Mitochondrial Processing Peptidase
chemical_list: D008666:Metalloendopeptidases; D011498:Protein Precursors; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D000096122:Mitochondrial Processing Peptidase