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How does the TOM complex mediate insertion of precursor proteins into the mitochondrial outer membrane?

Rapaport D - J. Cell Biol. (2005)

Bottom Line: A multisubunit translocase of the outer mitochondrial membrane (TOM complex) mediates both the import of mitochondrial precursor proteins into the internal compartments of the organelle and the insertion of proteins residing in the mitochondrial outer membrane.The proposed beta-barrel structure of Tom40, the pore-forming component of the translocase, raises the question of how the apparent uninterrupted beta-barrel topology can be compatible with a role of Tom40 in releasing membrane proteins into the lipid core of the bilayer.In this review, I discuss insertion mechanisms of proteins into the outer membrane and present alternative models based on the opening of a multisubunit beta-barrel TOM structure or on the interaction of outer membrane precursors with the outer face of the Tom40 beta-barrel structure.

View Article: PubMed Central - PubMed

Affiliation: Institute for Physiological Chemistry, Ludwig-Maximilians University, 81377 Munich, Germany. rapaport@med.uni-muenchen.de

ABSTRACT
A multisubunit translocase of the outer mitochondrial membrane (TOM complex) mediates both the import of mitochondrial precursor proteins into the internal compartments of the organelle and the insertion of proteins residing in the mitochondrial outer membrane. The proposed beta-barrel structure of Tom40, the pore-forming component of the translocase, raises the question of how the apparent uninterrupted beta-barrel topology can be compatible with a role of Tom40 in releasing membrane proteins into the lipid core of the bilayer. In this review, I discuss insertion mechanisms of proteins into the outer membrane and present alternative models based on the opening of a multisubunit beta-barrel TOM structure or on the interaction of outer membrane precursors with the outer face of the Tom40 beta-barrel structure.

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Is there a lateral opening of the TOM channel? (A) According to the lateral opening model, the precursor of outer membrane (OM) protein is inserted first into the lumen of the TOM channel. Next, there is a lateral opening of the translocation pore to release the TM segment to the lipid bilayer. (B) In this alternative model, the precursor interacts with the exposed domain of Tom40 and inserts into the interface between the outer face of the complex and the lipid bilayer. IMS, intermembrane space.
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fig2: Is there a lateral opening of the TOM channel? (A) According to the lateral opening model, the precursor of outer membrane (OM) protein is inserted first into the lumen of the TOM channel. Next, there is a lateral opening of the translocation pore to release the TM segment to the lipid bilayer. (B) In this alternative model, the precursor interacts with the exposed domain of Tom40 and inserts into the interface between the outer face of the complex and the lipid bilayer. IMS, intermembrane space.

Mentions: Another unlikely scenario involves a lateral opening of the β-barrel structure (Fig. 2 A). Such a model would require significant displacement of the β strands with respect to each other in order to allow the release of the α helix into the lipid core. However, because the overall structure of the barrel depends on interstrand hydrogen bonds, it is hard to envision such a disruption in the network of long-range hydrogen bonds without major structural destabilization. It is doubtful that these hydrogen bonds can be reformed in the low dielectric medium of the membrane. Altogether, this scenario involves the unlikely implication that each insertion of a helical membrane protein results in an irreversible destruction of the β-barrel structure of the translocation pore. Indeed, a lateral opening of any β-barrel structure has not been reported so far.


How does the TOM complex mediate insertion of precursor proteins into the mitochondrial outer membrane?

Rapaport D - J. Cell Biol. (2005)

Is there a lateral opening of the TOM channel? (A) According to the lateral opening model, the precursor of outer membrane (OM) protein is inserted first into the lumen of the TOM channel. Next, there is a lateral opening of the translocation pore to release the TM segment to the lipid bilayer. (B) In this alternative model, the precursor interacts with the exposed domain of Tom40 and inserts into the interface between the outer face of the complex and the lipid bilayer. IMS, intermembrane space.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171261&req=5

fig2: Is there a lateral opening of the TOM channel? (A) According to the lateral opening model, the precursor of outer membrane (OM) protein is inserted first into the lumen of the TOM channel. Next, there is a lateral opening of the translocation pore to release the TM segment to the lipid bilayer. (B) In this alternative model, the precursor interacts with the exposed domain of Tom40 and inserts into the interface between the outer face of the complex and the lipid bilayer. IMS, intermembrane space.
Mentions: Another unlikely scenario involves a lateral opening of the β-barrel structure (Fig. 2 A). Such a model would require significant displacement of the β strands with respect to each other in order to allow the release of the α helix into the lipid core. However, because the overall structure of the barrel depends on interstrand hydrogen bonds, it is hard to envision such a disruption in the network of long-range hydrogen bonds without major structural destabilization. It is doubtful that these hydrogen bonds can be reformed in the low dielectric medium of the membrane. Altogether, this scenario involves the unlikely implication that each insertion of a helical membrane protein results in an irreversible destruction of the β-barrel structure of the translocation pore. Indeed, a lateral opening of any β-barrel structure has not been reported so far.

Bottom Line: A multisubunit translocase of the outer mitochondrial membrane (TOM complex) mediates both the import of mitochondrial precursor proteins into the internal compartments of the organelle and the insertion of proteins residing in the mitochondrial outer membrane.The proposed beta-barrel structure of Tom40, the pore-forming component of the translocase, raises the question of how the apparent uninterrupted beta-barrel topology can be compatible with a role of Tom40 in releasing membrane proteins into the lipid core of the bilayer.In this review, I discuss insertion mechanisms of proteins into the outer membrane and present alternative models based on the opening of a multisubunit beta-barrel TOM structure or on the interaction of outer membrane precursors with the outer face of the Tom40 beta-barrel structure.

View Article: PubMed Central - PubMed

Affiliation: Institute for Physiological Chemistry, Ludwig-Maximilians University, 81377 Munich, Germany. rapaport@med.uni-muenchen.de

ABSTRACT
A multisubunit translocase of the outer mitochondrial membrane (TOM complex) mediates both the import of mitochondrial precursor proteins into the internal compartments of the organelle and the insertion of proteins residing in the mitochondrial outer membrane. The proposed beta-barrel structure of Tom40, the pore-forming component of the translocase, raises the question of how the apparent uninterrupted beta-barrel topology can be compatible with a role of Tom40 in releasing membrane proteins into the lipid core of the bilayer. In this review, I discuss insertion mechanisms of proteins into the outer membrane and present alternative models based on the opening of a multisubunit beta-barrel TOM structure or on the interaction of outer membrane precursors with the outer face of the Tom40 beta-barrel structure.

Show MeSH