Multistep assembly of the protein import channel of the mitochondrial outer membrane.
Proteins targeted to mitochondria are transported into the organelle through a high molecular weight complex called the translocase of the outer mitochondrial membrane (TOM). At the core of this machinery is a multisubunit general import pore (GIP) of 400 kDa. Here we report the assembly of the yeast GIP that involves two successive intermediates of 250 kDa and 100 kDa. The precursor of the channel-lining Tom40 is first targeted to the membrane via the receptor proteins Tom20 and Tom22; it then assembles with Tom5 to form the 250 kDa intermediate exposed to the intermembrane space. The 250 kDa intermediate is followed by the formation of the 100 kDa intermediate that associates with Tom6. Maturation to the 400 kDa complex occurs by association of Tom7 and Tom22. Tom7 functions by promoting both the dissociation of the 400 kDa complex and the transition from the 100 kDa intermediate to the mature complex. These results indicate that the dynamic conversion between the 400 kDa complex and the 100 kDa late intermediate allows integration of new precursor subunits into pre-existing complexes.
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Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg Germany.
Meisinger
C
C
Prinz
T
T
Wiedemann
N
N
Truscott
K N
KN
Pfanner
N
N
Ryan
M T
MT
D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000737:chemistry* / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D008954:Models, Biological; D008970:Molecular Weight; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D021381:Protein Transport; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
D002352:Carrier Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D011498:Protein Precursors; D021122:Protein Subunits; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; C489350:TOM20 protein, S cerevisiae; C090857:TOM22 protein, S cerevisiae; C106794:TOM5 protein, S cerevisiae; C099634:TOM7 protein, S cerevisiae; C084008:TOMM20 protein, human; C489971:TOMM22 protein, human; C066555:Tom40 protein, S cerevisiae