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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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A working model in which the two pores are surrounded by β-barrel structures. The TOM complex might contain eight molecules of Tom40. Each of these monomers is in a β-barrel topology, and they are organized in a double-ring structure in which two pores are each surrounded by five Tom40 molecules. Each green cylinder represents one molecule of Tom40. (A) The precursor of outer membrane (OM) protein is inserted first into one of these central pores. (B) Next, there is a rearrangement of the oligomeric structure, resulting in an opening between the subunits, which allows release of the αTM segment to the lipid bilayer. IMS, intermembrane space.
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fig3: A working model in which the two pores are surrounded by β-barrel structures. The TOM complex might contain eight molecules of Tom40. Each of these monomers is in a β-barrel topology, and they are organized in a double-ring structure in which two pores are each surrounded by five Tom40 molecules. Each green cylinder represents one molecule of Tom40. (A) The precursor of outer membrane (OM) protein is inserted first into one of these central pores. (B) Next, there is a rearrangement of the oligomeric structure, resulting in an opening between the subunits, which allows release of the αTM segment to the lipid bilayer. IMS, intermembrane space.

Mentions: An alternative model presents the TOM complex as an oligomer of eight β barrels surrounding two central cavities that are arranged in a double-ring shape (Fig. 3 A). Taking into account the findings that a dimer is the basic structural element of Tom40 (Dekker et al., 1998; Rapaport et al., 1998), this arrangement would suggest that four dimers are in one complex. The TOM complex was indeed suggested to harbor six to eight molecules of Tom40 (Dekker et al., 1998; Künkele et al., 1998), and electron microscopic visualization of the TOM complex revealed the presence of two to three pores (Künkele et al., 1998; Ahting et al., 1999; Model et al., 2002). Furthermore, several homo-oligomers of β-barrel proteins have been documented (Tamm et al., 2004). In such a model, the translocation pores would be in the center of the ring. According to this scenario, the αTM segment is first inserted into the central cavity of the ring (Fig. 3 A). Next, a rearrangement of the barrels results in the formation of a gate releasing the αTM segment into the lipid bilayer (Fig. 3 B). The reported major rearrangement of the TOM complex as a result of interaction with preprotein suggests that the translocase is indeed a dynamic complex (Rapaport et al., 1998). Such a scenario is appealing because a lateral opening of the β barrel itself is not required. Our observation that a matrix-destined preprotein does not compete with an αTM-containing precursor (Ahting et al., 2005) suggests a model in which the two pores are not functionally equivalent. Rather, matrix-destined precursors are translocated through a distinct pore from the one used by αTM-containing outer membrane proteins. An experimental support for such an assumption and, thereby, for the aforementioned model is currently missing.


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

Rapaport D - J. Cell Biol. (2005)

A working model in which the two pores are surrounded by β-barrel structures. The TOM complex might contain eight molecules of Tom40. Each of these monomers is in a β-barrel topology, and they are organized in a double-ring structure in which two pores are each surrounded by five Tom40 molecules. Each green cylinder represents one molecule of Tom40. (A) The precursor of outer membrane (OM) protein is inserted first into one of these central pores. (B) Next, there is a rearrangement of the oligomeric structure, resulting in an opening between the subunits, which allows release of the αTM segment to the lipid bilayer. IMS, intermembrane space.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: A working model in which the two pores are surrounded by β-barrel structures. The TOM complex might contain eight molecules of Tom40. Each of these monomers is in a β-barrel topology, and they are organized in a double-ring structure in which two pores are each surrounded by five Tom40 molecules. Each green cylinder represents one molecule of Tom40. (A) The precursor of outer membrane (OM) protein is inserted first into one of these central pores. (B) Next, there is a rearrangement of the oligomeric structure, resulting in an opening between the subunits, which allows release of the αTM segment to the lipid bilayer. IMS, intermembrane space.
Mentions: An alternative model presents the TOM complex as an oligomer of eight β barrels surrounding two central cavities that are arranged in a double-ring shape (Fig. 3 A). Taking into account the findings that a dimer is the basic structural element of Tom40 (Dekker et al., 1998; Rapaport et al., 1998), this arrangement would suggest that four dimers are in one complex. The TOM complex was indeed suggested to harbor six to eight molecules of Tom40 (Dekker et al., 1998; Künkele et al., 1998), and electron microscopic visualization of the TOM complex revealed the presence of two to three pores (Künkele et al., 1998; Ahting et al., 1999; Model et al., 2002). Furthermore, several homo-oligomers of β-barrel proteins have been documented (Tamm et al., 2004). In such a model, the translocation pores would be in the center of the ring. According to this scenario, the αTM segment is first inserted into the central cavity of the ring (Fig. 3 A). Next, a rearrangement of the barrels results in the formation of a gate releasing the αTM segment into the lipid bilayer (Fig. 3 B). The reported major rearrangement of the TOM complex as a result of interaction with preprotein suggests that the translocase is indeed a dynamic complex (Rapaport et al., 1998). Such a scenario is appealing because a lateral opening of the β barrel itself is not required. Our observation that a matrix-destined preprotein does not compete with an αTM-containing precursor (Ahting et al., 2005) suggests a model in which the two pores are not functionally equivalent. Rather, matrix-destined precursors are translocated through a distinct pore from the one used by αTM-containing outer membrane proteins. An experimental support for such an assumption and, thereby, for the aforementioned model is currently missing.

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